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Fischer OW, Justesen TF, Gögenur DS, Madsen MT, Mortensen MB, Gögenur I, Orhan A. Long-Term Oncological Outcomes of Granulocyte Colony-Stimulating Factor (G-CSF) Treatment in Gastrointestinal Cancers: A Systematic Review and Meta-Analysis. Cancers (Basel) 2025; 17:1313. [PMID: 40282489 PMCID: PMC12026166 DOI: 10.3390/cancers17081313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 04/09/2025] [Accepted: 04/10/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND Granulocyte-colony stimulating factor (G-CSF) prophylaxis is widely used in gastrointestinal (GI) cancers. The use of G-CSF in GI cancers has not previously been investigated systematically in a meta-analysis. Thus, we systematically reviewed the literature to describe the G-CSF use and potential influence on long-term oncological outcomes in GI cancers. METHOD The literature search of this systematic review and meta-analysis was conducted in PubMed, Embase, Cochrane Library and Web of Science. The PRISMA-P guidelines were followed. Studies that reported data on patients with GI cancers undergoing oncological treatment with G-CSF prophylaxis were included. Outcomes of interest were overall survival (OS), progression-free survival (PFS) and adverse events (AE), specifically neutropenia grade III/IV. A time-to-event random-effects meta-analysis was conducted. Risk of bias was assessed using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool for Randomized Controlled Trials (RoB) tool. FINDINGS In total, 2452 articles were screened for eligibility. Ultimately, 13 studies were included with a total patient number of 2673. The included studies indicated a positive association between OS and G-CSF prophylaxis (HR 0.72, 95% CI: 0.56-0.91, I2: 54%, low quality evidence). No significant relation between G-CSF use and PFS was found in the pooled analyses (HR 0.74, 95% CI: 0.51-1.08, I2: 73%, moderate quality evidence). However, a positive effect of G-CSF use was found in the retrospective cohorts reporting data on PFS (HR 0.50, 95% CI: 0.32-0.77, I2: 0%). A marked drop in neutropenia grade III/IV rates was observed in patients treated with G-CSF (risk ratio (RR) 0.46, 95% CI: 0.28-0.77, I2: 72%, high quality evidence). INTERPRETATION G-CSF prophylaxis provides a reduction in neutropenia grade III/IV in patients with GI cancers (high level of certainty) and a favorable OS (low certainty), while PFS is unaffected (moderate certainty). Studies on PFS and G-CSF use are nonetheless limited.
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Affiliation(s)
- Oliver Wedel Fischer
- Center for Surgical Science, Department of Surgery, Zealand University Hospital, 4600 Køge, Denmark (A.O.)
| | - Tobias Freyberg Justesen
- Center for Surgical Science, Department of Surgery, Zealand University Hospital, 4600 Køge, Denmark (A.O.)
| | - Dilara Seyma Gögenur
- Center for Surgical Science, Department of Surgery, Zealand University Hospital, 4600 Køge, Denmark (A.O.)
| | - Michael Tvilling Madsen
- Center for Surgical Science, Department of Surgery, Zealand University Hospital, 4600 Køge, Denmark (A.O.)
- Department of Surgery, Slagelse Sygehus, 4200 Slagelse, Denmark
| | - Michael Bau Mortensen
- Odense PIPAC Center, Odense University Hospital, 5000 Odense, Denmark
- Odense Pancreas Center (OPAC), Odense University Hospital, 5000 Odense, Denmark
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, 5000 Odense, Denmark
- Department of Surgery, Odense University Hospital, 5000 Odense, Denmark
| | - Ismail Gögenur
- Center for Surgical Science, Department of Surgery, Zealand University Hospital, 4600 Køge, Denmark (A.O.)
- Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Adile Orhan
- Center for Surgical Science, Department of Surgery, Zealand University Hospital, 4600 Køge, Denmark (A.O.)
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Fukumitsu N, Matsumoto Y, Chen L, Sugawara Y, Fujisawa N, Niiyama E, Ouchi S, Oe E, Saito T, Ebara M. Development of Layer-by-Layer Magnetic Nanoparticles for Application to Radiotherapy of Pancreatic Cancer. Molecules 2025; 30:1382. [PMID: 40142157 PMCID: PMC11946117 DOI: 10.3390/molecules30061382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 02/07/2025] [Accepted: 03/18/2025] [Indexed: 03/28/2025] Open
Abstract
Pancreatic cancer is among the deadliest malignancies, with few treatment options for locally advanced, unresectable cases. Conventional therapies, such as chemoradiotherapy and hyperthermia, show promise but face challenges in improving outcomes. This study introduces a novel drug delivery system using gemcitabine (GEM)-loaded layer-by-layer magnetic nanoparticles (LBL MNPs) combined with alternating magnetic field (AMF) application and X-ray irradiation to enhance therapeutic efficacy. LBL MNPs were synthesized using optimized layering techniques to achieve superior drug loading and controlled release. Human pancreatic cancer cells (PANC-1) were treated with LBL MNPs alone, with AMF-induced hyperthermia, and in combination with X-rays. The results demonstrate that the 7-layer LBL MNPs exhibited optimal cytotoxicity, significantly reducing cell viability at concentrations of 30 µg/mL and higher. Combining 7-layer LBL MNPs with AMF increased cell death in a time- and concentration-dependent manner, achieving up to 98% inhibition of cell proliferation. The addition of X-rays to the regimen demonstrated a strong synergistic effect, resulting in a 13-fold increase in cell death compared to controls. These findings highlight the potential of this integrated approach to improve outcomes in patients with pancreatic cancer.
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Affiliation(s)
| | - Yoshitaka Matsumoto
- Department of Radiation Oncology, Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan;
- Proton Medical Research Center, University of Tsukuba Hospital, Tsukuba 305-8576, Japan;
| | - Lili Chen
- Smart Polymers Group, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science, Tsukuba 305-0044, Japan; (L.C.); (N.F.); (S.O.); (E.O.); (M.E.)
| | - Yu Sugawara
- Proton Medical Research Center, University of Tsukuba Hospital, Tsukuba 305-8576, Japan;
| | - Nanami Fujisawa
- Smart Polymers Group, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science, Tsukuba 305-0044, Japan; (L.C.); (N.F.); (S.O.); (E.O.); (M.E.)
| | - Eri Niiyama
- Smart Polymers Group, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science, Tsukuba 305-0044, Japan; (L.C.); (N.F.); (S.O.); (E.O.); (M.E.)
| | - Sosuke Ouchi
- Smart Polymers Group, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science, Tsukuba 305-0044, Japan; (L.C.); (N.F.); (S.O.); (E.O.); (M.E.)
| | - Emiho Oe
- Smart Polymers Group, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science, Tsukuba 305-0044, Japan; (L.C.); (N.F.); (S.O.); (E.O.); (M.E.)
| | - Takashi Saito
- Department of Radiation Oncology, Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan;
- Proton Medical Research Center, University of Tsukuba Hospital, Tsukuba 305-8576, Japan;
| | - Mitsuhiro Ebara
- Smart Polymers Group, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science, Tsukuba 305-0044, Japan; (L.C.); (N.F.); (S.O.); (E.O.); (M.E.)
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Jung K, Choi S, Song H, Kwak K, Anh S, Jung JH, Kim B, Ahn J, Kim J, Hwang JH, Lee JC. Real-world dose reduction of standard and modified FOLFIRINOX in metastatic pancreatic cancer: a systematic review, evidence-mapping, and meta-analysis. Ther Adv Med Oncol 2023; 15:17588359231175441. [PMID: 37441327 PMCID: PMC10333643 DOI: 10.1177/17588359231175441] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Accepted: 04/25/2023] [Indexed: 07/15/2023] Open
Abstract
Background FOLFIRINOX, used in metastatic pancreatic cancer (MPC), is highly efficacious but also toxic. Various dose modifications for FOLFIRINOX have been introduced to reduce toxicity. However, these studies lack a unified pattern for 'planned' dose modification, and the 'actually administered' dose varied more. Objective To map a 10-year trend for 'planned' and 'actual' doses of FOLFIRINOX and investigate the clinical outcomes according to dose modification. Data sources and methods A comprehensive systematic literature search was conducted from January 2011 to September 2021. All studies for FOLFIRINOX as first-line treatment in MPC were considered. Selected studies were firstly classified according to prospective versus retrospective research, secondly standard versus modified FOLFIRINOX, and thirdly 'planned' versus 'actual' dose. For evidence-mapping for the trend of dose modification, we developed a web-based interactive bubble-plot program (www.RDI-map.com). Objective response rate (ORR) and hematologic toxicity were set as endpoints for the comparison of clinical outcomes according to dose modification. Results A total of 37 studies were identified for evidence-mapping (11 prospective and 26 retrospective studies). There were 12 different types of 'planned' dose modification in FOLFIRINOX ranging 75-100% oxaliplatin, 75-100% irinotecan, 0-100% 5-fluorouracil (5-FU) bolus, and 75-133% 5-FU continuous injection. The 'actual' dose further decreased to 54-96%, 61-88%, 0-92%, and 63-98%, respectively. For the standard versus modified FOLFIRINOX, the ORR was 28.2% (95% CI: 22.5-33.9%) and 33.8% (95% CI: 30.3-37.3%), respectively (p = 0.100), and the incidence of febrile neutropenia was 11.6% (95% CI: 0-16.0%) and 5.5% (95% CI: 0-8.9%), respectively (p = 0.030). Conclusions RDI-map.com enables multifactorial evidence-mapping for practical FOLFIRINOX dose reduction. The pattern of dose modification was not consistent across studies, and there was a significant gap between the 'planned' and 'actual' doses. Modified FOLFIRINOX showed similar efficacy to the standard regimen with reduced incidence of febrile neutropenia.
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Affiliation(s)
| | | | - Hyunjoo Song
- School of Computer Science and Engineering,
Soongsil University, Seoul, Korea
| | - Kyuhan Kwak
- School of Computer Science and Engineering,
Soongsil University, Seoul, Korea
| | - Soyeon Anh
- Division of Statistics, Medical Research
Collaborating Center, Seoul National University Bundang Hospital, Seongnam,
Korea
| | - Jae Hyup Jung
- Department of Internal Medicine, Seoul National
University Bundang Hospital, Seongnam, Korea
| | - Bomi Kim
- Department of Internal Medicine, Seoul National
University Bundang Hospital, Seongnam, Korea
| | - Jinwoo Ahn
- Department of Internal Medicine, Seoul National
University Bundang Hospital, Seongnam, Korea
| | - Jaihwan Kim
- Department of Internal Medicine, Seoul National
University Bundang Hospital, Seongnam, Korea
- College of Medicine, Seoul National
University, Seoul, Korea
| | - Jin-Hyeok Hwang
- Department of Internal Medicine, Seoul
National University Bundang Hospital, Seongnam, Korea
- College of Medicine, Seoul National
University, Seoul, Korea
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Optimizing First-Line Chemotherapy in Metastatic Pancreatic Cancer: Efficacy of FOLFIRINOX versus Nab-Paclitaxel Plus Gemcitabine. Cancers (Basel) 2023; 15:cancers15020416. [PMID: 36672366 PMCID: PMC9856679 DOI: 10.3390/cancers15020416] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 01/05/2023] [Accepted: 01/06/2023] [Indexed: 01/11/2023] Open
Abstract
Pancreatic cancer (PC) is one of the most lethal tumors in Europe with an overall 5-year survival rate of 5%. Since 1992, gemcitabine (Gem) has been the treatment of choice for metastatic disease with significant improvement in median overall survival (OS) compared to fluorouracil. A good performance status (PS) at diagnosis appears to be a strong predictive factor for better survival. Overall, 50% of PC are metastatic or locally advanced at diagnosis, and more than 70% of the resected patients will experience a recurrence, with a median OS ranging from 4 to 10 months (mos). FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and Nab-paclitaxel (Nab-p) plus Gem have recently increased survival of patients with metastatic PC, over Gem. Treatment with FOLFIRINOX is generally considered more effective with respect to the doublet, with toxicity concerns, FOLFIRINOX achieves an overall response rate (ORR) of 31.6%, while for Nab-p plus Gem ORR is 23%; however, FOLFIRINOX was associated with higher rates of grade 3 and higher adverse events. Although the international guidelines indicate that both regimens can be used as first-line therapy for patients with metastatic PC, FOLFIRINOX is the most widely used; Nab-p plus Gem is more frequently used in patients with lower PS. In this review, we critically analyze these two regimens to give a pragmatic guide to treatment options.
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Carvalho de Brito AB, Riechelmann RP, Fonseca de Jesus VH. Impact of Granulocyte Colony-Stimulating Factor (G-CSF) on the Outcomes of Patients With Metastatic Pancreatic Adenocarcinoma (MPA) During First-Line Treatment With FOLFIRINOX: A Single-Center Retrospective Analysis. Cancer Control 2023; 30:10732748221149543. [PMID: 36592369 PMCID: PMC9829887 DOI: 10.1177/10732748221149543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
INTRODUCTION The role of primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF) for patients with metastatic pancreatic adenocarcinoma (MPA) treated with FOLFIRINOX is unknown. We aimed to compare the frequencies of grades 3 or 4 neutropenia (G3/4N) and febrile neutropenia (FN) and survival outcomes according to the use of PP. METHODS This is a retrospective study. We included patients with pathologically confirmed MPA treated with FOLFIRINOX in first-line. Patients who received primary prophylaxis (PP group) were compared to patients who received secondary or no G-CSF (no-PP group). Overall survival (OS) and progression-free survival (PFS) were evaluated using the standard Cox proportional hazard model. To account for potential biases, we performed sensitivity analyses excluding patients who received secondary prophilaxis and treating G-CSF as a time-dependent covariate in extended Cox proportional hazard models. RESULTS The study population consisted of 123 patients. PP was used by 75 patients (61.0%). G3/4 N occurred more frequently among patients without PP (10.7 vs 41.7%; P < .001). There was no difference in the frequency of FN between groups (5.3 vs 8.3%; P = .710). In multivariate analysis, PP was associated with a trend toward improved OS (HR = .66; 95% confidence interval [95% CI] .41 - 1.07; P = .094). In the multivariate model excluding patients with secondary prophylaxis (HR = .54; 95% CI 0.32 - .91; P = .022) and in the time-dependent model (HR = .47; 95% CI 0.28 - .80; P = .005), PP was associated with statistically superior OS. CONCLUSIONS Despite the reduction in the frequency of G3/4N, the risk of FN among patients treated with FOLFIRINOX without G-CSF is too low to justify its use in a routine basis. However, given the potential of G-CSF to improve survival in this setting, further studies are warranted to assess its role during treatment with FOLFIRINOX for patients with MPA.
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Affiliation(s)
| | | | - Victor Hugo Fonseca de Jesus
- Medical Oncology Department, AC Camargo Cancer Center, Sao Paulo, Brazil,Victor Hugo Fonseca de Jesus, MD, MSc, Medical Oncology Department, AC Camargo Cancer Center, Rua Prof. Antonio Prudente, 211, Sao Paulo 01509-010, Brazil.
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Hatachi Y, Mohan SR, Kotake T, Satake H, Okita Y, Yasui H, Tsuji A. FOLFIRINOX as First-line Chemotherapy in Japanese Patients Suffering from Metastatic Pancreatic Cancer (KOBE FOLFIRINOX Study). CANCER DIAGNOSIS & PROGNOSIS 2022; 2:101-106. [PMID: 35400007 PMCID: PMC8962842 DOI: 10.21873/cdp.10083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 12/09/2021] [Indexed: 06/14/2023]
Abstract
BACKGROUND/AIM FOLFIRINOX (oxaliplatin, irinotecan, 5-fluorouracil, and leucovorin) combination chemotherapy is the gold-standard therapy for advanced pancreatic cancer. In this study, FOLFIRINOX dosages for Japanese patients were established enabling FOLFIRINOX therapy optimization for efficient use. PATIENTS AND METHODS Patients with advanced pancreatic cancer were treated with varying doses of FOLFIRINOX to determine the optimum dosage for highest remission outcomes with the least post-chemotherapy toxicities. RESULTS Patients given 180 mg of irinotecan and a 400 mg bolus of 5-fluorouracil (5-FU) showed a marked difference in outcome when compared to irinotecan 180 mg given without the 5-FU bolus, with the overall response rate being 28%, a survival time of 6.4 months and progression-free survival time of 4.5 months. CONCLUSION The optimum dose of FOLFIRINOX was a dosage combination of oxaliplatin 85 mg/m 2 , irinotecan 180 mg/m 2 , l-leucovorin 400 mg/m 2 and 5-FU 2,400 mg/m 2 , administered as a continuous 46-h infusion.
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Affiliation(s)
- Yukimasa Hatachi
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
- Department of Clinical Oncology, Kansai Rosai Hospital, Amagasaki, Japan
| | - Sharad R Mohan
- Department of Artificial Intelligence, AI Medical and Health Tech Systems, Osaka, Japan
| | - Takeshi Kotake
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
- Department of Clinical Oncology, Kansai Electric Power Hospital, Osaka, Japan
| | - Hironaga Satake
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
- Cancer Treatment Center, Kansai Medical University Hospital, Hirakata, Japan
| | - Yoshihiro Okita
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
- Department of Clinical Oncology, Kagawa University Hospital, Kagawa, Japan
| | - Hisateru Yasui
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Akihito Tsuji
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
- Department of Clinical Oncology, Kagawa University Hospital, Kagawa, Japan
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Nitipir C, Vrabie R, Parosanu AI, Tulin R, Cretu B, Cursaru A, Slavu I, Miron A, Calu V, Orlov Slavu MC. Clinical Impact of the Administration of FOLFIRINOX Beyond Six Months in Advanced Pancreatic Adenocarcinoma: A Cohort Study. Cureus 2021; 13:e19361. [PMID: 34925974 PMCID: PMC8654089 DOI: 10.7759/cureus.19361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/08/2021] [Indexed: 11/14/2022] Open
Abstract
Background Although a toxic regimen, FOLFIRINOX is one of the most efficient chemotherapy regimens in advanced pancreatic adenocarcinoma. There is no standard number of cycles in locally advanced or metastatic stages. Materials and method The present retrospective study reports the experience of a single center with this regimen administered until disease progression or unacceptable toxicity. The authors of this retrospective study analyzed the data on patients with this diagnosis treated in our clinic during 2017-2021. Forty-two patients were included in the study, 21 who received six courses or less and 21 who received more than six courses. Progression-free survival (PFS) and overall survival (OS) were analyzed according to this stratification. The oncological response was also reported according to dose reduction and treatment delay, irrespective of the number of courses administered. Results Median PFS was 7.5 months, and median OS was 13.6 months in the entire studied population. When patients were compared according to the number of courses received (under six vs. over six), there were obvious differences (PFS: 5.17 months vs. 11.2, p = 0.8, OS: 8 months vs. 17.3 months, p = 0.6). However, when stratifying survival by treatment delay and the presence or absence of dose reduction, better results were seen with lower doses (p<0.001) and treatment temporization (p=0.03). The general incidence of hematologic and neurologic toxicity was higher than the ones reported in the literature. Conclusion The study revealed that patients benefit from the administration of FOLFIRINOX for more than six months, but that the administration of full dose and the maintaining dose intensity does not necessarily favor the patient.
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Affiliation(s)
- Cornelia Nitipir
- Oncology, Elias Emergency University Hospital, Bucharest, ROU.,Oncology, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
| | - Radu Vrabie
- Oncology, Elias Emergency University Hospital, Bucharest, ROU.,Oncology, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
| | - Andreea Ioana Parosanu
- Oncology, Elias Emergency University Hospital, Bucharest, ROU.,Oncology, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
| | - Raluca Tulin
- Endocrinology, Emergency Hospital Prof. Dr. Agrippa Ionescu, Bucharest, ROU
| | - Bogdan Cretu
- Orthopedics and Traumatology, University Emergency Hospital Bucharest, Bucharest, ROU.,Orthopedics, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
| | - Adrian Cursaru
- Orthopedics and Traumatology, University Emergency Hospital Bucharest, Bucharest, ROU.,Orthopedics, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
| | - Iulian Slavu
- Surgery, Emergency Hospital Prof. Dr. Agrippa Ionescu, Bucharest, ROU
| | - Adrian Miron
- Surgery, Elias Emergency University Hospital, Bucharest, ROU
| | - Valentin Calu
- Surgery, Elias Emergency University Hospital, Bucharest, ROU
| | - Maria Cristina Orlov Slavu
- Oncology, Elias Emergency University Hospital, Bucharest, ROU.,Oncology, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
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Chen J, Hua Q, Wang H, Zhang D, Zhao L, Yu D, Pi G, Zhang T, Lin Z. Meta-analysis and indirect treatment comparison of modified FOLFIRINOX and gemcitabine plus nab-paclitaxel as first-line chemotherapy in advanced pancreatic cancer. BMC Cancer 2021; 21:853. [PMID: 34301232 PMCID: PMC8306351 DOI: 10.1186/s12885-021-08605-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Accepted: 07/16/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Modified FOLFIRINOX and gemcitabine plus nab-paclitaxel (GEM-NAB) have been recommended as first-line therapies for advanced pancreatic cancer (PC). Due to the lack of evidence to directly compare them, we conducted this network meta-analysis to indirectly compare the effectiveness and toxicity of modified FOLFIRINOX and GEM-NAB. METHODS The eligible retrospective studies on treatments related to modified FOLFIRINOX and GEM-NAB up to 4 April 2020 were searched and assessed. We used the frequentist model to analyze the survival and toxicity data between different treatments. Pooled analysis for overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and events of toxicity were analyzed in this study. RESULTS Twenty-two studies were involved in this network meta-analysis. The comparisons on OS and PFS showed that modified FOLFIRINOX and GEM-NAB had similar treatment efficacy (OS: 1.13; 95% CI: 0.78-1.63; PFS: HR: 1.19; 95% CI: 0.85-1.67). GEM-NAB was more effective than modified FOLFIRINOX based on the result of ORR (RR: 1.43; 95% CI: 1.04-1.96). Moreover, our analysis showed a similar toxicity profile between modified FOLFIRINOX and GEM-NAB. CONCLUSIONS The current evidence showed that modified FOLFIRINOX and GEM-NAB were similar in survival and toxicity. Many factors should be considered for in the formulation of optimal treatment, and our meta-analysis could provide some guidance to treatment selection in the first-line setting for advanced PC.
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Affiliation(s)
- Jiayuan Chen
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Qingling Hua
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Haihong Wang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Dejun Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Lei Zhao
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Dandan Yu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Guoliang Pi
- Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430079, China
| | - Tao Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Zhenyu Lin
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Vary A, Lebellec L, Di Fiore F, Penel N, Cheymol C, Rad E, El Hajbi F, Lièvre A, Edeline J, Bimbai AM, Le Deley MC, Turpin A. FOLFIRINOX relative dose intensity and disease control in advanced pancreatic adenocarcinoma. Ther Adv Med Oncol 2021; 13:17588359211029825. [PMID: 34349842 PMCID: PMC8287268 DOI: 10.1177/17588359211029825] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 06/14/2021] [Indexed: 01/05/2023] Open
Abstract
Background: Most patients with advanced pancreatic adenocarcinoma (PA) treated with FOLFIRINOX experience adverse events requiring dose reduction. We aimed to assess the association between relative dose intensity (RDI) and disease control in a European setting. Methods: We retrospectively included patients with advanced PA treated with three or more cycles of FOLFIRINOX between 2011 and 2018 in six French centers. We computed the cumulative single-agent RDI (csRDI) before the first reassessment for each FOLFIRINOX agent (oxaliplatin, irinotecan, 5FU bolus, and 5FU intravenous infusion) and the cumulative multi-drug RDI (cmRDI) of their combination. The association between RDI and disease control or objective response at first reassessment was evaluated using multivariable logistic regression models controlling for performance status, liver metastases, and center. Results: We included 243 patients. Median csRDIs were 81%, 79%, 75%, and 85% for oxaliplatin, irinotecan, 5FU bolus, and 5FU intravenous infusion, respectively. Median cmRDI was 80%. None of the RDIs was significantly associated with disease control or objective response. Including RDI in a clinical model did not improve its ability to predict disease control; the area under the curve was 0.79 (95% CI: 0.73–0.85) with RDI versus 0.78 (95% CI: 0.72–0.85) without. Similar results were observed for the objective response. Conclusion: Pragmatic dose adjustments of FOLFIRINOX should be made by oncologists without considering a loss of effect.
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Affiliation(s)
| | | | | | | | - Claire Cheymol
- Onco-Hematology Department, Saint Vincent de Paul Hospital, Lille, France
| | - Emilia Rad
- Medical Oncology Department, Victor Provo Hospital, Roubaix, France
| | - Farid El Hajbi
- Medical Oncology Department, Oscar Lambret Center, Lille, France
| | - Astrid Lièvre
- Department of Gastroenterology, CHU Pontchaillou, Rennes, France
| | - Julien Edeline
- Medical Oncology Department, Eugène Marquis Center, Rennes, France
| | | | | | - Anthony Turpin
- University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020 - UMR-S 1277 - Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, Lille, France
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10
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Zhang B, Zhou F, Hong J, Ng DM, Yang T, Zhou X, Jin J, Zhou F, Chen P, Xu Y. The role of FOLFIRINOX in metastatic pancreatic cancer: a meta-analysis. World J Surg Oncol 2021; 19:182. [PMID: 34154596 PMCID: PMC8218408 DOI: 10.1186/s12957-021-02291-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 06/04/2021] [Indexed: 12/20/2022] Open
Abstract
Background The prognosis of pancreatic cancer (PC) is extremely poor, and most patients with metastatic PC still receive palliative care. Here, we report the efficacy and safety of FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, 5-fluorouracil) in the treatment of metastatic PC. Methods We searched PubMed, Web of Science, EBSCO, and Cochrane library databases for articles that described efficacy and safety of FOLFIRINOX in patients with metastatic PC, from January 1996 to July 2020. The primary outcomes targeted included overall survival (OS) and progression-free survival (PFS). Results We found that FOLFIRINOX could directly improve OS rate of patients with metastatic PC (HR 0.76, 95% Cl 0.67–0.86, p<0.001) but had no benefit on PFS. Results from subgroup analyses showed that FOLFIRINOX had superior benefits than monochemotherapy (HR 0.59, 95% Cl 0.52–0.67, p<0.001), followed by FOLFIRINOX versus combination chemotherapy (HR 0.76, 95% Cl 0.61–0.95, p<0.001). The result of FOLFIRINOX versus nab-paclitaxel + gemcitabine had no benefit (HR 0.91, 95% Cl 0.82–1.02, p>0.05). The main adverse events (AEs) targeted hematological toxicity and the gastrointestinal system, and included febrile neutropenia, a reduction in white blood cells and appetite, as well as diarrhea. Conclusion These findings indicated that FOLFIRINOX has potential benefits for the prognosis of patients with metastatic PC. Furthermore, there is no difference between the regimen of FOLFIRINOX and nab-paclitaxel + gemcitabine in this study. The application of FOLFIRINOX should be according to the actual situation of the patients and the experience of the doctors. Graphical abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s12957-021-02291-6.
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Affiliation(s)
- Beilei Zhang
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Fengyan Zhou
- Emergency Medical Center, Ningbo Yinzhou No 2 Hospital, Ningbo, Zhejiang, China
| | - Jiaze Hong
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Derry Minyao Ng
- Medical College of Ningbo University, Ningbo, Zhejiang, China
| | - Tong Yang
- Department of Tumor HIFU Therapy, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China
| | - Xinyu Zhou
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Jieyin Jin
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Feifei Zhou
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Ping Chen
- Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China
| | - Yunbao Xu
- Department of Radiotherapy and Chemotherapy, Hwamei Hospital, University of Chinese Academy of Sciences, Northwest Street 41, Haishu District, Ningbo, 315010, Zhejiang, China.
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11
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Giommoni E, Maiello E, Vaccaro V, Rondini E, Vivaldi C, Tortora G, Toppo L, Giordano G, Latiano TP, Lamperini C, Pillozzi S, Boni L, Antonuzzo L, Di Costanzo F. Activity and Safety of NAB-FOLFIRI and NAB-FOLFOX as First-Line Treatment for metastatic Pancreatic Cancer (NabucCO Study). Curr Oncol 2021; 28:1761-1772. [PMID: 34066784 PMCID: PMC8161763 DOI: 10.3390/curroncol28030164] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 04/30/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Relevant improvement in first-line treatment of metastatic pancreatic cancer (mPC) was provided by FOLFIRINOX and by gemcitabine (gem) plus nab-paclitaxel (Nab-p) regimens. Regardless of the first-line treatment survival benefit, most patients survive less than 1 year. AIM The objectives of this multicenter phase I/II study were to evaluate as first-line chemotherapy (CT) two modified regimens of FOLFIRINOX, replacing either oxaliplatin (Oxa) or irinotecan with Nab-p, in patients with mPC. METHODS The primary objectives of phase 1 were the definition of the dose limit binations, while for phase II they were the characterization of safety and activity of Nab-FOLFIRI and Nab-FOLFOX in mPC. RESULTS Sixty-three patients received Nab-FOLFIRI or Nab-FOLFOX in phase I. We defined MTD at 120 mg/m2 for Nab-p with FOLFIRI and 160 mg/m2 with FOLFOX. In phase II, we randomized 42 patients for each arm with the following results: (1) overall response rate (ORR) was 31% for both schedules; (2) a clinical benefit rate (CBR) of 69% and 71%; (3) 1-year survival was 41% and 50%; (4) progression free survival (PFS) was 6 months and 5.6 months; (5) median overall survival (OS) was 10.2 and 10.4 months for Nab-FOLFIRI and Nab-FOLFOX, respectively. (6) Neutropenia was the most common grade ≥3 adverse event in our regimens, significantly lower than that reported for the FOLFIRINOX triplet. CONCLUSION Nab-FOLFIRI and Nab-FOLFOX might be hopeful first-line CT options for mPC patients, with promising activity and a good safety profile.
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Affiliation(s)
- Elisa Giommoni
- Medical Oncology Unit, Careggi University Hospital, 50134 Florence, Italy; (C.L.); (S.P.); (L.A.); (F.D.C.)
| | - Evaristo Maiello
- Medical Oncology Unit, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy; (E.M.); (T.P.L.)
| | - Vanja Vaccaro
- Medical Oncology Unit, Istituto Nazionale Tumori Regina Elena, 00144 Roma, Italy;
| | - Ermanno Rondini
- Oncology Unit, Ospedale Santa Maria Nuova—IRCCS, 42100 Reggio Emilia, Italy;
| | - Caterina Vivaldi
- Medical Oncology Unit 2, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy;
| | - Giampaolo Tortora
- Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata, 37134 Verona, Italy;
| | - Laura Toppo
- Medical Oncology Unit, ASST Cremona, 26100 Cremona, Italy;
| | - Guido Giordano
- Oncology Unit, Ospedale “Sacro Cuore di Gesù” Fatebenefratelli, 82100 Benevento, Italy;
| | - Tiziana Pia Latiano
- Medical Oncology Unit, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy; (E.M.); (T.P.L.)
| | - Cinzia Lamperini
- Medical Oncology Unit, Careggi University Hospital, 50134 Florence, Italy; (C.L.); (S.P.); (L.A.); (F.D.C.)
| | - Serena Pillozzi
- Medical Oncology Unit, Careggi University Hospital, 50134 Florence, Italy; (C.L.); (S.P.); (L.A.); (F.D.C.)
| | - Luca Boni
- Clinical Trial Coordinating Center, Careggi University Hospital, 50134 Florence, Italy;
| | - Lorenzo Antonuzzo
- Medical Oncology Unit, Careggi University Hospital, 50134 Florence, Italy; (C.L.); (S.P.); (L.A.); (F.D.C.)
| | - Francesco Di Costanzo
- Medical Oncology Unit, Careggi University Hospital, 50134 Florence, Italy; (C.L.); (S.P.); (L.A.); (F.D.C.)
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12
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Vienot A, Chevalier H, Bolognini C, Gherga E, Klajer E, Meurisse A, Jary M, Kim S, d’Engremont C, Nguyen T, Calcagno F, Almotlak H, Fein F, Nasri M, Abdeljaoued S, Turpin A, Borg C, Vernerey D. FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study. World J Gastrointest Oncol 2020; 12:332-346. [PMID: 32206183 PMCID: PMC7081111 DOI: 10.4251/wjgo.v12.i3.332] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2019] [Revised: 12/26/2019] [Accepted: 01/14/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND FOLFIRINOX regimen is the first-line reference chemotherapy (L1) in advanced pancreatic ductal adenocarcinoma (aPDAC). FOLFOXIRI, a schedule with a lower dose of irinotecan and no bolus 5-fluorouracil, has demonstrated efficacy and feasibility in colorectal cancer.
AIM To investigate the potential clinical value of FOLFOXIRI in patients with aPDAC in routine clinical practice.
METHODS Analyses were derived from all consecutive aPDAC patients treated in L1 between January 2011 and December 2017 in two French institutions, with either FOLFOXIRI (n = 165) or FOLFIRINOX (n = 124) regimens. FOLFOXIRI consisted of irinotecan (165 mg/m2), oxaliplatin (85 mg/m2), leucovorin (200 mg/m2) and 5-fluorouracil (3200 mg/m2 as a 48-h continuous infusion) every 2 wk. Ninety-six pairs of patients were selected through propensity score matching, and clinical outcomes of the two treatment regimens were compared.
RESULTS Median overall survival was 11.1 mo in the FOLFOXIRI and 11.6 mo in the FOLFIRINOX cohorts, respectively. After propensity score matching, survival rates remained similar between the two regimens in terms of overall survival (hazard ratio = 1.22; P = 0.219) and progression-free survival (hazard ratio = 1.27; P = 0.120). The objective response rate was 37.1% in the FOLFOXIRI group vs 47.8% in the FOLFIRINOX group (P = 0.187). Grade 3/4 toxicities occurred in 28.7% of patients in the FOLFOXIRI cohort vs 19.5% in the FOLFIRINOX cohort (P = 0.079). FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events. Hematopoietic growth factors were used after each chemotherapy cycle and the low hematological toxicity rates were below 5% with both regimens.
CONCLUSION FOLFOXIRI is feasible in L1 in patients with aPDAC but does not confer any therapeutic benefit as compared with FOLFIRINOX. The low hematological toxicity rates strengthened the relevance of primary prophylaxis with hematopoietic growth factors.
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Affiliation(s)
- Angélique Vienot
- Department of Medical Oncology, Besançon University Hospital, Besançon F-25030, France
- University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon F-25000, France
- INSERM CIC-1431, Clinical Investigation Center in Biotherapy, Besançon University Hospital, Besançon F-25030, France
| | - Hortense Chevalier
- Department of Medical Oncology, Lille University Hospital, Lille F-59000, France
| | - Clément Bolognini
- Department of Medical Oncology, Besançon University Hospital, Besançon F-25030, France
| | - Elisabeta Gherga
- Department of Medical Oncology, Nord Franche-Comté Hospital, Montbéliard F-25020, France
| | - Elodie Klajer
- Department of Medical Oncology, Besançon University Hospital, Besançon F-25030, France
| | - Aurélia Meurisse
- University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon F-25000, France
- Methodological and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon F-25030, France
| | - Marine Jary
- Department of Medical Oncology, Besançon University Hospital, Besançon F-25030, France
- University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon F-25000, France
- INSERM CIC-1431, Clinical Investigation Center in Biotherapy, Besançon University Hospital, Besançon F-25030, France
| | - Stefano Kim
- Department of Medical Oncology, Besançon University Hospital, Besançon F-25030, France
- University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon F-25000, France
- INSERM CIC-1431, Clinical Investigation Center in Biotherapy, Besançon University Hospital, Besançon F-25030, France
| | | | - Thierry Nguyen
- Department of Medical Oncology, Besançon University Hospital, Besançon F-25030, France
| | - Fabien Calcagno
- Department of Medical Oncology, Besançon University Hospital, Besançon F-25030, France
| | - Hamadi Almotlak
- Department of Medical Oncology, Besançon University Hospital, Besançon F-25030, France
| | - Francine Fein
- Department of Gastroenterology, Besançon University Hospital, Besançon F-25030, France
| | - Meher Nasri
- Department of Medical Oncology, Nord Franche-Comté Hospital, Montbéliard F-25020, France
| | - Syrine Abdeljaoued
- University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon F-25000, France
| | - Anthony Turpin
- Department of Medical Oncology, Lille University Hospital, Lille F-59000, France
| | - Christophe Borg
- Department of Medical Oncology, Besançon University Hospital, Besançon F-25030, France
- University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon F-25000, France
- INSERM CIC-1431, Clinical Investigation Center in Biotherapy, Besançon University Hospital, Besançon F-25030, France
| | - Dewi Vernerey
- University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon F-25000, France
- Methodological and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon F-25030, France
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13
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Yamao K, Takenaka M, Yoshikawa T, Ishikawa R, Okamoto A, Yamazaki T, Nakai A, Omoto S, Kamata K, Minaga K, Hagiwara S, Sakurai T, Nishida N, Chiba Y, Watanabe T, Kudo M. Clinical Safety and Efficacy of Secondary Prophylactic Pegylated G-CSF in Advanced Pancreatic Cancer Patients Treated with mFOLFIRINOX: A Single-center Retrospective Study. Intern Med 2019; 58:1993-2002. [PMID: 30996164 PMCID: PMC6702006 DOI: 10.2169/internalmedicine.2234-18] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Objective Although modified FOLFIRINOX (mFOLFIRINOX, mFFX) is widely used for patients with advanced pancreatic ductal adenocarcinoma (PDAC), maintenance of the standard dose intensity is often difficult due to the high incidence of neutropenic events. Pegylated granulocyte colony-stimulating factor (G-CSF) (Peg G) is a long-lasting G-CSF agent that is applicable for prophylaxis against neutropenic complications. The aim of this study was to assess the clinical safety and efficacy of mFFX combined with secondary prophylaxis using Peg G in advanced PDAC patients. Methods Advanced PDAC patients who had received more than two cycles of mFFX were analyzed. The clinical safety and efficacy were compared between patients in the Peg G group and those in the non-Peg G group in a retrospective manner. Results Among 45 patients treated with mFFX, 28 exhibited grade 3-4 neutropenia or febrile neutropenia. Among these 28 patients, 4 who received only 1 or 2 mFFX cycles were excluded from this study. Finally, 11 patients in the Peg G group and 13 in the non-Peg G group were enrolled. The combination therapy with Peg G and mFFX markedly prolonged the progression-free survival compared with the non-Peg G group, and its effects were associated with a reduced incidence of neutropenic events as well as lower rates of dosage reduction, delayed chemotherapy due to neutropenic events and altered blood cell counts after chemotherapy. Conclusion The scheduled administration of secondary prophylactic Peg G prolonged the progression-free survival in patients treated with mFFX. The combination therapy of Peg G and mFFX may be recommended in patients who exhibit grade 3-4 neutropenic events after prior mFFX cycles.
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Affiliation(s)
- Kentaro Yamao
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Mamoru Takenaka
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Tomoe Yoshikawa
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Rei Ishikawa
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Ayana Okamoto
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Tomohiro Yamazaki
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Atsushi Nakai
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Shunsuke Omoto
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Ken Kamata
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Kosuke Minaga
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Satoru Hagiwara
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Toshiharu Sakurai
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Naoshi Nishida
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Yasutaka Chiba
- Clinical Research Center, Kindai University Hospital, Japan
| | - Tomohiro Watanabe
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
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14
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Cavanna L, Stroppa EM, Citterio C, Mordenti P, Di Nunzio C, Peveri S, Orlandi E, Vecchia S. Modified FOLFIRINOX for unresectable locally advanced/metastatic pancreatic cancer. A real-world comparison of an attenuated with a full dose in a single center experience. Onco Targets Ther 2019; 12:3077-3085. [PMID: 31118666 PMCID: PMC6498392 DOI: 10.2147/ott.s200754] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Accepted: 03/06/2019] [Indexed: 12/18/2022] Open
Abstract
Purpose: Metastatic pancreatic adenocarcinoma has a very poor prognosis. Although irinotecan, oxaliplatin and leucovorin-modulated fluorouracil (FOLFIRINOX) significantly increases survival in advanced pancreatic cancer, compared to employing only gemcitabine (GEM), toxicities have tempered enthusiasm for its use. Methods: This study retrospectively analyses the real-world clinical practice with full and attenuated doses of FOLFIRINOX in unselected patients with locally advanced unresectable or metastatic pancreatic cancer, treated at an Italian general hospital. Efficacy, tolerability, and toxicity were evaluated, and overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier method. Results: Fifty consecutive patients with advanced (13) or metastatic (37) pancreatic adenocarcinomas were treated with FOLFIRINOX at the Medical Oncology Unit, Piacenza General Hospital, North Italy. The first enrolled consecutive 18 patients (36%) of this series started the treatment with a full dose of the regimen, while the subsequent 32 (64%) consecutive patients received dose attenuation (-20% bolus fluorouracil and -25% irinotecan). In the entire group, the response rate, median OS, and median PFS were 30%, 10.1 months, and 5.6 months, respectively, with no differences in objective response in the 32 patients that received an attenuated dose compared with the 18 patients receiving a full dose of chemotherapy. However, neutropenia, anemia, fatigue, and vomiting were statistically increased in the 18 patients receiving a full dose compared with the 32 patients receiving an attenuated dose of FOLFIRINOX (p<0.05). Conclusion: This study demonstrates the efficacy and tolerability of modified FOLFIRINOX in advanced and metastatic pancreatic cancer.
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Affiliation(s)
- Luigi Cavanna
- Oncology and Hematology Department, Oncology Unit, Piacenza General Hospital, Piacenza, Italy
| | - Elisa Maria Stroppa
- Oncology and Hematology Department, Oncology Unit, Piacenza General Hospital, Piacenza, Italy
| | - Chiara Citterio
- Oncology and Hematology Department, Oncology Unit, Piacenza General Hospital, Piacenza, Italy
| | - Patrizia Mordenti
- Oncology and Hematology Department, Oncology Unit, Piacenza General Hospital, Piacenza, Italy
| | - Camilla Di Nunzio
- Oncology and Hematology Department, Oncology Unit, Piacenza General Hospital, Piacenza, Italy
| | - Silvia Peveri
- Allergology and Statistics Unit, Piacenza General Hospital, Piacenza, Italy
| | - Elena Orlandi
- Oncology and Hematology Department, Oncology Unit, Piacenza General Hospital, Piacenza, Italy
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15
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Hiroshima Y, Fukumitsu N, Saito T, Numajiri H, Murofushi KN, Ohnishi K, Nonaka T, Ishikawa H, Okumura T, Sakurai H. Concurrent chemoradiotherapy using proton beams for unresectable locally advanced pancreatic cancer. Radiother Oncol 2019; 136:37-43. [PMID: 31015127 DOI: 10.1016/j.radonc.2019.03.012] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Revised: 02/25/2019] [Accepted: 03/11/2019] [Indexed: 12/25/2022]
Abstract
BACKGROUND AND PURPOSE We investigated clinical outcomes of proton beam concurrent chemoradiotherapy (CCRT) for unresectable, locally advanced pancreatic cancer (LAPC) patients. MATERIALS AND METHODS Records from 42 unresectable LAPC patients (21 male and 21 female, 39-83 years old) with IIB/III clinical staging of 1/41 treated by proton beam CCRT were retrospectively reviewed. Twelve patients received a conventional 50 Gray equivalents (GyE) in 25 fractions protocol and 30 others received a higher dose protocol of 54.0-67.5 GyE in 25-33 fractions. Gemcitabine or S-1 (Tegafur, Gimeracil and Oteracil) was used concurrently. Toxicity, overall survival (OS) and local control (LC) were examined. RESULTS Acute adverse events of grades 1, 2, 3 and 4 were found in 4, 15, 17 and 2 patients, respectively. All grade 3 and 4 events were hematologic. Late adverse events of grades 1 and 2 were found in 3 and 2 patients, respectively. No late adverse effects of grade 3 or higher were observed. The 1-year/2-year OS rates from the start of CCRT were 77.8/50.8% with median survival time (MST) of 25.6 months. The 1-year/2-year LC rate from CCRT start was 83.3/78.9% with a median time to local recurrence of more than 36 months. Total irradiation dose was the only significant factor in univariate analyses of OS and LC (p = 0.015 and 0.023, respectively). CONCLUSION Proton beam CCRT lengthened survival periods compared to previous photon CCRT data and higher dose irradiation prolonged LC and OS for unresectable LAPC patients. Proton beam therapy is therefore safe and effective in these cases.
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Affiliation(s)
- Yuichi Hiroshima
- Proton Medical Research Center, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
| | - Nobuyoshi Fukumitsu
- Proton Medical Research Center, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8575, Japan
| | - Takashi Saito
- Proton Medical Research Center, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8575, Japan
| | - Haruko Numajiri
- Proton Medical Research Center, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8575, Japan
| | - Keiko Nemoto Murofushi
- Proton Medical Research Center, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8575, Japan
| | - Kayoko Ohnishi
- Proton Medical Research Center, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8575, Japan
| | - Tetsuo Nonaka
- Proton Medical Research Center, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8575, Japan
| | - Hitoshi Ishikawa
- Proton Medical Research Center, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8575, Japan
| | - Toshiyuki Okumura
- Proton Medical Research Center, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8575, Japan
| | - Hideyuki Sakurai
- Proton Medical Research Center, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8575, Japan
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16
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Eraslan E, Yildiz F, Tufan G, Aslan F, Demirci U, Oksuzoglu OB. First line modified Folfirinox versus gemcitabine for advanced pancreatic cancer: A single institution retrospective experience. JOURNAL OF ONCOLOGICAL SCIENCES 2019. [DOI: 10.1016/j.jons.2019.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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17
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Ulusakarya A, Teyar N, Karaboué A, Haydar M, Krimi S, Biondani P, Gumus Y, Chebib A, Almohamad W, Morère JF. Patient-tailored FOLFIRINOX as first line treatment of patients with advanced pancreatic adenocarcinoma. Medicine (Baltimore) 2019; 98:e15341. [PMID: 31008993 PMCID: PMC6494255 DOI: 10.1097/md.0000000000015341] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
FOLFIRINOX is one of the most effective reference regimens in the 1st line treatment of locally advanced (LA) and metastatic pancreatic cancer (mPC), despite its high toxicity. We evaluated our real-life experience with "patient-tailored intent to treat FOLFIRINOX" in patients with LA or mPC compared to other reports along with the pivotal phase III trial.We analyzed data from all consecutive patients with pancreatic ductal adenocarcinoma treated with dose-modified FOLFIRINOX in 2016 at Paul Brousse University Hospital. Irinotecan was administered whenever initial serum bilirubin was <1.5 × upper limit of normal. Oxaliplatin was stopped for severe sensory neuropathy. Initial dose reductions were made according to patient profile (eg, age, comorbidities) and later due to toxicity. The treatment was continued until surgery or disease progression. Endpoints were time to progression (TTP), overall survival (OS), objective response rate (ORR), and secondary complete resection (R0R1).Thirty-seven patients with unresectable LA or mPC received patient-tailored FOLFIRINOX as 1st line chemotherapy. There were 22 male (59%) and 15 female patients (41%) aged 44 to 81 years with LA (18 patients, 49%) and mPC (19 patients, 51%). They had World Health Organization-performance status of 0 (59%) or 1 (41%). A total of 384 cycles were administered. Median dose intensities (mg/m/w) were 28.9 for oxaliplatin, 56.8 for irinotecan, and 886.2 for 5-fluorouracil. Thirty-four patients were assessed for response; ORR and disease control rates were 47% and 85%, respectively. R0R1 rate was 30%. Median TTP and OS were 9.6 and 14.6 months. LA disease was associated with significantly longer TTP and OS (P < .001).FOLFIRINOX with patient-tailored dose adaptations seems to offer better results in patients with advanced PC. This approach in the neoadjuvant setting results in a macroscopic R0R1 in 61% of patients with initially unresectable disease. It deserves prospective evaluation to further improve outcomes in the management of advanced PC.
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Affiliation(s)
- Ayhan Ulusakarya
- Assistance Publique-Hôpitaux de Paris, Department of Medical Oncology, Paul Brousse Hospital
- INSERM U935 Campus CNRS, Villejuif
| | - Nahla Teyar
- Assistance Publique-Hôpitaux de Paris, Department of Medical Oncology, Paul Brousse Hospital
| | - Abdoulaye Karaboué
- INSERM U935 Campus CNRS, Villejuif
- Medical Oncology Unit, GHI Le Raincy-Montfermeil, Montfermeil, France
| | - Mazen Haydar
- Assistance Publique-Hôpitaux de Paris, Department of Medical Oncology, Paul Brousse Hospital
| | - Sarra Krimi
- Assistance Publique-Hôpitaux de Paris, Department of Medical Oncology, Paul Brousse Hospital
| | - Pamela Biondani
- Assistance Publique-Hôpitaux de Paris, Department of Medical Oncology, Paul Brousse Hospital
| | - Yusuf Gumus
- Assistance Publique-Hôpitaux de Paris, Department of Medical Oncology, Paul Brousse Hospital
| | - Amale Chebib
- Assistance Publique-Hôpitaux de Paris, Department of Medical Oncology, Paul Brousse Hospital
| | - Wathek Almohamad
- Assistance Publique-Hôpitaux de Paris, Department of Medical Oncology, Paul Brousse Hospital
| | - Jean-François Morère
- Assistance Publique-Hôpitaux de Paris, Department of Medical Oncology, Paul Brousse Hospital
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Li X, Guo C, Li Q, Wei S, Zhang Q, Chen Y, Shen Y, Ma T, Li G, Gao S, Que R, Lou J, Yu R, Yuan Y, Wei Q, Huang P, Liang T, Bai X. Association of Modified-FOLFIRINOX-Regimen-Based Neoadjuvant Therapy with Outcomes of Locally Advanced Pancreatic Cancer in Chinese Population. Oncologist 2019; 24:301-e93. [PMID: 30459238 PMCID: PMC6519772 DOI: 10.1634/theoncologist.2018-0696] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 10/08/2018] [Indexed: 12/27/2022] Open
Abstract
LESSONS LEARNED Modification of FOLFIRINOX significantly improves safety and tolerability in Chinese patients with locally advanced pancreatic cancer.Patients with locally advanced pancreatic cancer benefit from neoadjuvant therapy and experience a much better survival than patients with upfront surgery. BACKGROUND The objective of this study was to evaluate the efficacy of modified-FOLFIRINOX (mFOLFIRINOX) regimens in Chinese patients with locally advanced pancreatic cancer (LAPC) and to compare outcomes between patients with LAPC treated with mFOLFIRINOX-based neoadjuvant therapy (LAPC-N) and patients with LAPC who underwent upfront surgery (LAPC-S). METHODS Forty-one patients with LAPC-N were enrolled prospectively. Imaging features, chemotherapy response, adverse events, perioperative complications, histology, and survival were analyzed. Seventy-four patients with resectable pancreatic cancer (RPC) (from April 2012 to November 2017) and 19 patients with LAPC-S (from April 2012 to March 2014) were set as observational cohorts, and data were collected retrospectively. LAPC-N patients with adequate response underwent surgical treatment, whereas continuous chemotherapy was given to LAPC-N patients who were not deemed resectable after treatment, and the response was re-evaluated every 2 months. RESULTS Forty-one patients with LAPC received mFOLFIRINOX with a response rate of 37.1%. The most common severe adverse events were neutropenia and anemia. mFOLFIRINOX-based neoadjuvant therapy contributed to a remarkable decrease in CA19-9 level and tumor diameter. Fourteen LAPC-N patients underwent surgery (LAPC-N-S) after downstaging. Compared with LAPC-N-S cases, LAPC-S patients had longer operative time, more blood loss, and a higher risk of grade 5 complications. The median overall survival (OS) and progression-free survival (PFS) of LAPC-N-S patients were 27.7 months and 19.3 months, respectively, which were similar to those of patients with RPC (30.0 months and 23.0 months) and much longer than those of patients with LAPC-S (8.9 months and 7.6 months), respectively. CONCLUSION Neoadjuvant chemotherapy such as the mFOLFIRINOX regimen can be recommended for Chinese patients with LAPC after dose modification. Patients with LAPC-N who underwent surgery obtained significantly improved survival compared with patients in the observational LAPC-S cohort, who did not undergo neoadjuvant therapy.
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Affiliation(s)
- Xiang Li
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Chengxiang Guo
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Qinghai Li
- Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Shumei Wei
- Department of Pathology, the Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Qi Zhang
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Yiwen Chen
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Yinan Shen
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Tao Ma
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Guogang Li
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Shunliang Gao
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Risheng Que
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Jianying Lou
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Risheng Yu
- Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Ying Yuan
- Department of Medical Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Qichun Wei
- Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Pintong Huang
- Department of Ultrasound Medicine, the Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine
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Chung MJ, Kang H, Kim HG, Hyun JJ, Lee JK, Lee KH, Noh MH, Kang DH, Lee SH, Bang S, Pancreatobiliary Cancer Study Group of Korean Society of Gastrointestinal Cancer. Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer. World J Gastrointest Oncol 2018; 10:505-515. [PMID: 30595804 PMCID: PMC6304301 DOI: 10.4251/wjgo.v10.i12.505] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 10/24/2018] [Accepted: 11/25/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To evaluate the efficacy and safety of modified FOLFIRINOX as a second-line treatment for gemcitabine (GEM)-refractory unresectable pancreatic cancer (PC). METHODS This study was a prospective, multicenter, one-arm, open-label, phase II trial. Patients with unresectable PC, who showed disease progression during GEM-based chemotherapy were enrolled. All patients were administered FOLFIRINOX with reduced irinotecan and oxaliplatin (RIO; irinotecan 120 mg/m2 and oxaliplatin 60 mg/m2), which was set according to the phase I study of FOLFIRINOX. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events were evaluated. Additionally, changes in quality of life (QoL) were assessed using a questionnaire on QoL. RESULTS Between August 2015 and May 2016, a total of 48 patients were enrolled. The median follow-up time was 259 d with a median of 8.5 cycles. The ORR and DCR were 18.8% and 62.5%, respectively, including one patient who showed complete remission. The median PFS was 5.8 mo [95% confidence interval (CI): 3.7-7.9] and median OS was 9.0 mo (95%CI: 6.4-11.6). Neutropenia (64.6%) was the most common grade 3-4 adverse event, followed by febrile neutropenia (16.7%). Although 14.6% of patients experienced grade 3 fatigue, most non-hematologic AEs were under grade 2. In the QoL analysis, the global health status score before treatment was not different from the score at the last visit after treatment (45.43 ± 22.88 vs 48.66 ± 24.14, P = 0.548). CONCLUSION FOLFIRINOX with RIO showed acceptable toxicity and promising efficacy for GEM-refractory unresectable PC. However, this treatment requires careful observation of treatment-related hematologic toxicities.
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Affiliation(s)
- Moon Jae Chung
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, South Korea
| | - Huapyong Kang
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, South Korea
| | - Ho Gak Kim
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu 42471, South Korea
| | - Jong Jin Hyun
- Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan 15355, South Korea
| | - Jun Kyu Lee
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang 10326, South Korea
| | - Kwang Hyuck Lee
- Division of Gastroenterology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea
| | - Myung Hwan Noh
- Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, South Korea
| | - Dae Hwan Kang
- Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, South Korea
| | - Sang Hyub Lee
- Departments of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, South Korea
| | - Seungmin Bang
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, South Korea
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Severe Neutropenia is Associated with Better Clinical Outcomes in Patients with Advanced Pancreatic Cancer Who Receive Modified FOLFIRINOX Therapy. Cancers (Basel) 2018; 10:cancers10110454. [PMID: 30453583 PMCID: PMC6265962 DOI: 10.3390/cancers10110454] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 10/19/2018] [Accepted: 11/14/2018] [Indexed: 12/13/2022] Open
Abstract
While modified FOLFIRINOX therapy is effective for treating advanced pancreatic cancer, it frequently causes severe neutropenia. The present study investigated the effect of severe neutropenia on clinical outcomes in advanced pancreatic cancer patients who received modified FOLFIRINOX. The study subjects were 51 patients (30 males and 21 females) with advanced pancreatic cancer who received modified FOLFIRINOX (2h bolus injection of oxaliplatin at 85 mg/m², 2 h bolus injection of L-leucovorin at 200 mg/m², 90min bolus injection of irinotecan at 150 mg/m², followed by continuous infusion of 5-fluorouracil for 46 h at 2400 mg/m² without bolus 5-fluorouracil) during the period from January 2014 to May 2018. No patients had prior history of chemotherapy. Adverse events, including neutropenia, were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Median overall survival (OS) was the primary endpoint, while median time to treatment failure (TTF), overall response rate (ORR), and the incidence of other adverse events were secondary endpoints. Severe neutropenia (grade ≥3) occurred in 39 patients (76.4%), and Cox proportional hazard analysis identified high total bilirubin level as a significant risk factor. Median duration of OS was significantly longer in patients with severe neutropenia than in those without it (21.3 months versus 8.9 months, p = 0.020). Moreover, there was a significant correlation between OS and the grade of neutropenia (r = 0.306, p = 0.029). ORR tended to be higher, though not significantly, in patients with severe neutropenia. In contrast, the incidence rates of other adverse events were not different between the two groups. Severe neutropenia is an independent predictor of prognosis in advanced pancreatic cancer patients received modified FOLFIRINOX therapy.
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Kang H, Jo JH, Lee HS, Chung MJ, Bang S, Park SW, Song SY, Park JY. Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer. World J Gastrointest Oncol 2018; 10:421-430. [PMID: 30487953 PMCID: PMC6247105 DOI: 10.4251/wjgo.v10.i11.421] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 09/07/2018] [Accepted: 10/10/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To directly compare the efficacy and toxicity of standard-dose FOLFIRINOX (sFOLFIRINOX) and modified-dose FOLFIRINOX (mFOLFIRINOX, 75% of standard-dose) for pancreatic cancer. METHODS One hundred and thirty pancreatic cancer patients who received sFOLFIRINOX (n = 88) or mFOLFIRINOX (n = 42) as their first-line chemotherapy from January 2013 to July 2017 were retrospectively reviewed. For efficacy analysis, the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated and compared using Pearson's chi-square test, Kaplan-Meier plot and log-rank test. The adverse events (AEs) were evaluated, and severe (≥ grade 3) AEs rates of the two groups were compared for toxicity analysis. RESULTS The mFOLFIRINOX group included more female patients (30.7% vs 57.1%; P = 0.004) and older patients [age (median), 57 vs 63.5; P = 0.018] than the sFOLFIRINOX group. In the efficacy analysis, the ORR and DCR were not significantly different between the two groups (ORR: 39.8% vs 35.7%; P = 0.656; DCR: 80.7% vs 83.3%; P = 0.716). The median PFS and OS were also not different between the groups (PFS: 8.7 mo vs 8.1 mo, P = 0.272; OS: 13.9 mo vs 13.7 mo, P = 0.476). In the safety analysis with severe AEs, the rates of neutropenia (83.0% vs 66.7%; P = 0.044), anorexia (48.9% vs 28.6%; P = 0.029) and diarrhea (13.6% vs 0.0%; P = 0.009) were markedly lower in the mFOLFIRINOX group. CONCLUSION mFOLFIRINOX showed comparable efficacy but better safety compared to sFOLFIRINOX. If clinically necessary, initiating FOLFIRINOX with 75% of the standard-dose can alleviate toxicity concerns without compromising efficacy.
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Affiliation(s)
- Huapyong Kang
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul 03722, South Korea
| | - Jung Hyun Jo
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul 03722, South Korea
| | - Hee Seung Lee
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul 03722, South Korea
| | - Moon Jae Chung
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul 03722, South Korea
| | - Seungmin Bang
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul 03722, South Korea
| | - Seung Woo Park
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul 03722, South Korea
| | - Si Young Song
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul 03722, South Korea
| | - Jeong Youp Park
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul 03722, South Korea
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Matsumoto K, Kato H, Horiguchi S, Tsutsumi K, Saragai Y, Takada S, Mizukawa S, Muro S, Uchida D, Tomoda T, Okada H. Efficacy and safety of chemotherapy after endoscopic double stenting for malignant duodenal and biliary obstructions in patients with advanced pancreatic cancer: a single-institution retrospective analysis. BMC Gastroenterol 2018; 18:157. [PMID: 30367599 PMCID: PMC6203985 DOI: 10.1186/s12876-018-0886-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Accepted: 10/16/2018] [Indexed: 01/05/2023] Open
Abstract
Background Advanced pancreatic cancer is accompanied not only by bile duct obstruction, but also occasionally by duodenal obstruction. With new advances in chemotherapy and improvement in the management of stent dysfunction, the life expectancy of patients with pancreatic cancer has increased. This study aimed to evaluate the efficacy and safety of chemotherapy for advanced pancreatic cancer, as well as to analyze the prognostic factors, following endoscopic double stenting. Methods This retrospective study was conducted from January 1, 2007 to October 31, 2015 at an academic center. Fifty consecutive patients with pancreatic cancer who had undergone endoscopic double stenting, comprising duodenal and biliary stenting, were analyzed. We reviewed the patients records and analyzed the data of stent dysfunction rates after double stenting, reintervention for stent dysfunction, chemotherapy after double stenting, adverse events associated with chemotherapy after double stenting, survival times following double stenting, and overall survival times. The hospital’s institutional review board for human research approved this study. Results The overall survival time and the survival time following double stenting were 10.9 months (IQR 6.0–18.4 months) and 2.4 months (IQR 1.4–5.2 months), respectively. After double stenting, duodenal stent dysfunction occurred in 6 patients (12%), and biliary stent dysfunction occurred in 12 patients (24%), respectively. All patients who experienced stent dysfunction underwent endoscopic reintervention, and all of the procedures were successful. Twenty-one (42%) patients were treated with chemotherapy post double stenting; 9 patients received chemotherapy as a first-line treatment, 9 as a second-line treatment, and 3 as a third-line treatment. During chemotherapy, 8 (38%) patients had grade 3–4 adverse events, which were manageable. Chemotherapy post double stenting (OR, 0.19; 95% CI, 0.059–0.60; P = .0051), reintervention for biliary stent dysfunction (OR, 0.21; 95% CI, 0.081–0.50; P = .0002), and performance status (< 2) (OR, 0.28; 95% CI, 0.098–0.71; P = .0064) were significant prognostic factors after double stenting. Conclusions Systemic chemotherapy was manageable, even in patients with double stenting. Chemotherapy after double stenting and appropriate reintervention for stent obstructions potentially prolonged the survival of patients with advance pancreatic cancer.
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Affiliation(s)
- Kazuyuki Matsumoto
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan.
| | - Hironari Kato
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan
| | - Shigeru Horiguchi
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan
| | - Koichiro Tsutsumi
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan
| | - Yosuke Saragai
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan
| | - Saimon Takada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan
| | - Sho Mizukawa
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan
| | - Shinichiro Muro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan
| | - Daisuke Uchida
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan
| | - Takeshi Tomoda
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan
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de Jesus VHF, Camandaroba MPG, Donadio MDS, Cabral A, Muniz TP, de Moura Leite L, Sant'Ana LF. Retrospective comparison of the efficacy and the toxicity of standard and modified FOLFIRINOX regimens in patients with metastatic pancreatic adenocarcinoma. J Gastrointest Oncol 2018; 9:694-707. [PMID: 30151266 PMCID: PMC6087866 DOI: 10.21037/jgo.2018.04.02] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Accepted: 03/23/2018] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND FOLFIRINOX stands a major breakthrough in the management of metastatic pancreatic adenocarcinoma (MPA). Nonetheless, significant side-effects have been reported using standard FOLFIRINOX. We aimed to compare survival outcomes, response rates and toxicity of patients treated with standard or modified FOLFIRINOX in MPA. METHODS We included patients aged ≥18 years old, with pathologically confirmed MPA, treated with FOLFIRINOX in the first-line setting. Patients submitted to at least one cycle of full-dose FOLFIRINOX were grouped in the standard FOLFIRINOX group. RESULTS Patients treated with standard FOLFIRINOX were younger and had less comorbidity. We observed no differences in overall survival or in progression-free survival between the two treatment arms. The only variable independently associated with OS was log10[neutrophil-to-lymphocyte ratio (NLR)]. Modified FOLFIRINOX was associated with a lower dose reduction rate, but a slightly increased incidence of severe toxicity. CONCLUSIONS Modified FOLFIRINOX presents the same activity against MPA as standard FOLFIRINOX. We found no significant differences in toxicity, possibly due to patient selection and a higher dose reduction rate in the standard FOLFIRINOX arm. NLR stood as an important prognostic marker and further research is needed to comprehend its biological meaning in pancreatic cancer.
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Affiliation(s)
| | | | | | - Audrey Cabral
- Department of Medical Oncology, A.C. Camargo Cancer Center, São Paulo, SP, Brazil
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The benefits of modified FOLFIRINOX for advanced pancreatic cancer and its induced adverse events: a systematic review and meta-analysis. Sci Rep 2018; 8:8666. [PMID: 29875415 PMCID: PMC5989209 DOI: 10.1038/s41598-018-26811-9] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Accepted: 05/11/2018] [Indexed: 01/05/2023] Open
Abstract
FOLFIRINOX has been one of the first-line options for advanced pancreatic cancer, even though it induces significant adverse effects. Several institutions have begun using modified FOLFIRINOX to decrease its side effects and increase its tolerability. We systematically investigated the outcome from patients who initially received modified FOLFIRINOX as a chemotherapy regimen for advanced pancreatic cancer. We used the random-model generic inverse variance method to analyse the binary data with 95% confidence intervals (CIs). Eleven studies were included in the meta-analysis with 563 total patients. The 6-month and 1-year overall survival (OS) rates of locally advanced pancreatic cancer (LAPC) were 90.9% and 76.2%. The 6-month and 1-year progression-free survival (PFS) rates of LAPC were 81.5% and 48.5%. The 6-month and 1-year OS rates of metastatic pancreatic cancer (MPC) were 79.7% and 47.6%. The 6-month and 1-year PFS rates of MPC were 56.3% and 20.6%. The following rates were also calculated: complete response rate (CR): 2.9%; partial response rate (PR): 35.9%; stable disease rate (SD): 41.2%; overall response rate (OR): 34.6%; disease control rate (DCR): 76.7%; progressive disease: 23.1%; and grade III/IV adverse events (AEs): neutropenia 23.1%, febrile neutropenia 4.8%, thrombocytopenia 4.8%, anaemia 5.7%, fatigue 11.5%, nausea 9.1%, diarrhoea 10.1%, vomiting 5.7%, neuropathy 3.8%, and increased ALT 5.7%. In conclusion, modified FOLFIRINOX could provide comparative survival benefits with fewer adverse events compared to the conventional dosage.
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Kim JH, Lee SC, Oh SY, Song SY, Lee N, Nam EM, Lee S, Hwang IG, Lee HR, Lee KT, Bae SB, Kim HJ, Jang JS, Lim DH, Lee HW, Kang SY, Kang JH. Attenuated FOLFIRINOX in the salvage treatment of gemcitabine-refractory advanced pancreatic cancer: a phase II study. Cancer Commun (Lond) 2018; 38:32. [PMID: 29866170 PMCID: PMC5993129 DOI: 10.1186/s40880-018-0304-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2017] [Accepted: 01/05/2018] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Combination therapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) chemotherapy drastically improves survival of advanced pancreatic cancer patients. However, the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively. We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer. METHODS A multicenter phase II prospective open-label, single-arm study was conducted at 14 hospitals. Patients with histologically proven invasive ductal pancreatic adenocarcinoma, a measurable or evaluable lesion, Eastern Cooperative Oncology Group performance status 0 or 1, adequate organ function, and aged 19 years or older were eligible. Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m2, irinotecan 135 mg/m2, and leucovorin 400 mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000 mg/m2 continuously infused intravenously over 46 h on days 1-2, repeated every 2 weeks. The primary endpoint was progression-free survival from the initiation of FOLFIRINOX. Secondary endpoints were the objective response rate, disease control rate, overall survival, safety, and tolerability. We estimated overall survival and progression-free survival using the Kaplan-Meier methods. RESULTS We enrolled 39 patients from 14 institutions. The objective response rate was 10.3%, while the disease control rate was 64.1%. The 6-month and 1-year overall survival rates were 59.0% and 15.4%, respectively. Median progression-free survival and overall survival were 3.8 months (95% confidence interval [CI] 1.5-6.0 months) and 8.5 months (95% CI 5.6-11.4 months), respectively. Grade 3 or 4 adverse events were neutropenia (41.0%), nausea (10.3%), anorexia (10.3%), anemia (7.7%), mucositis (7.7%), pneumonia/pleural effusion (5.1%), and fatigue (5.1%). One treatment-related death attributable to septic shock occurred. CONCLUSION Attenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancreatic cancer.
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Affiliation(s)
- Jung Hoon Kim
- Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University, 15 Jinju-daero 816beon-gil, Jinju, 52727 Republic of Korea
| | - Sang-Cheol Lee
- Divsion of Hematology and Oncology, Department of Internal Medicine, Soonchunhyang University Hospital Cheonan, Cheonan, 31151 Republic of Korea
| | - Sung Yong Oh
- Department of Internal Medicine, Dong-A University Hospital, Busan, 49201 Republic of Korea
| | - Seo-Young Song
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, 24289 Republic of Korea
| | - Namsu Lee
- Divsion of Hematology and Oncology, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Seoul, 04401 Republic of Korea
| | - Eun Mi Nam
- Department of Internal Medicine, Ewha Womans University, College of Medicine, Seoul, 07985 Republic of Korea
| | - Soonil Lee
- Department of Internal Medicine, Dankook University Hospital, Cheonan, 31116 Republic of Korea
| | - In Gyu Hwang
- Department of Internal Medicine, Chung-Ang University, College of Medicine, Seoul, 06973 Republic of Korea
| | - Hyo Rak Lee
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Korea Cancer Hospital, Seoul, 01812 Republic of Korea
| | - Kyu Taek Lee
- Divsion of Hematology and Oncology, Department of Internal Medicine, Soonchunhyang University Hospital Cheonan, Cheonan, 31151 Republic of Korea
| | - Sang-Byung Bae
- Divsion of Hematology and Oncology, Department of Internal Medicine, Soonchunhyang University Hospital Cheonan, Cheonan, 31151 Republic of Korea
| | - Han Jo Kim
- Divsion of Hematology and Oncology, Department of Internal Medicine, Soonchunhyang University Hospital Cheonan, Cheonan, 31151 Republic of Korea
| | - Joung Soon Jang
- Department of Internal Medicine, Chung-Ang University, College of Medicine, Seoul, 06973 Republic of Korea
| | - Do Hyoung Lim
- Department of Internal Medicine, Dankook University Hospital, Cheonan, 31116 Republic of Korea
| | - Hyun Woo Lee
- Department of Hematology-Oncology, Ajou University Hospital, Suwon, 16499 Republic of Korea
| | - Seok Yun Kang
- Department of Hematology-Oncology, Ajou University Hospital, Suwon, 16499 Republic of Korea
| | - Jung Hun Kang
- Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University, 15 Jinju-daero 816beon-gil, Jinju, 52727 Republic of Korea
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Lowery MA, Ptashkin R, Jordan E, Berger MF, Zehir A, Capanu M, Kemeny NE, O'Reilly EM, El-Dika I, Jarnagin WR, Harding JJ, D'Angelica MI, Cercek A, Hechtman JF, Solit DB, Schultz N, Hyman DM, Klimstra DS, Saltz LB, Abou-Alfa GK. Comprehensive Molecular Profiling of Intrahepatic and Extrahepatic Cholangiocarcinomas: Potential Targets for Intervention. Clin Cancer Res 2018; 24:4154-4161. [PMID: 29848569 DOI: 10.1158/1078-0432.ccr-18-0078] [Citation(s) in RCA: 397] [Impact Index Per Article: 56.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Revised: 05/04/2018] [Accepted: 05/18/2018] [Indexed: 12/21/2022]
Abstract
Purpose: Various genetic driver aberrations have been identified among distinct anatomic and clinical subtypes of intrahepatic and extrahepatic cholangiocarcinoma, and these molecular alterations may be prognostic biomarkers and/or predictive of drug response.Experimental Design: Tumor samples from patients with cholangiocarcinoma who consented prospectively were analyzed using the MSK-IMPACT platform, a targeted next-generation sequencing assay that analyzes all exons and selected introns of 410 cancer-associated genes. Fisher exact tests were performed to identify associations between clinical characteristics and genetic alterations.Results: A total of 195 patients were studied: 78% intrahepatic and 22% extrahepatic cholangiocarcinoma. The most commonly altered genes in intrahepatic cholangiocarcinoma were IDH1 (30%), ARID1A (23%), BAP1 (20%), TP53 (20%), and FGFR2 gene fusions (14%). A tendency toward mutual exclusivity was seen between multiple genes in intrahepatic cholangiocarcinoma including TP53:IDH1, IDH1:KRAS, TP53:BAP1, and IDH1:FGFR2 Alterations in CDKN2A/B and ERBB2 were associated with reduced survival and time to progression on chemotherapy in patients with locally advanced or metastatic disease. Genetic alterations with potential therapeutic implications were identified in 47% of patients, leading to biomarker-directed therapy or clinical trial enrollment in 16% of patients.Conclusions: Cholangiocarcinoma is a genetically diverse cancer. Alterations in CDKN2A/B and ERBB2 are associated with negative prognostic implications in patients with advanced disease. Somatic alterations with therapeutic implications were identified in almost half of patients. These prospective data provide a contemporary benchmark for guiding the development of targeted therapies in molecularly profiled cholangiocarcinoma, and support to the use of molecular profiling to guide therapy selection in patients with advanced biliary cancers. Clin Cancer Res; 24(17); 4154-61. ©2018 AACR.
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Affiliation(s)
| | - Ryan Ptashkin
- Memorial Sloan Kettering Cancer Center, New York, New York
| | - Emmet Jordan
- Memorial Sloan Kettering Cancer Center, New York, New York
| | | | - Ahmet Zehir
- Memorial Sloan Kettering Cancer Center, New York, New York
| | | | - Nancy E Kemeny
- Memorial Sloan Kettering Cancer Center, New York, New York.,Weill Cornell Medical College, New York, New York
| | - Eileen M O'Reilly
- Memorial Sloan Kettering Cancer Center, New York, New York.,Weill Cornell Medical College, New York, New York
| | - Imane El-Dika
- Memorial Sloan Kettering Cancer Center, New York, New York
| | - William R Jarnagin
- Memorial Sloan Kettering Cancer Center, New York, New York.,Weill Cornell Medical College, New York, New York
| | - James J Harding
- Memorial Sloan Kettering Cancer Center, New York, New York.,Weill Cornell Medical College, New York, New York
| | - Michael I D'Angelica
- Memorial Sloan Kettering Cancer Center, New York, New York.,Weill Cornell Medical College, New York, New York
| | - Andrea Cercek
- Memorial Sloan Kettering Cancer Center, New York, New York.,Weill Cornell Medical College, New York, New York
| | | | - David B Solit
- Memorial Sloan Kettering Cancer Center, New York, New York.,Weill Cornell Medical College, New York, New York
| | | | - David M Hyman
- Memorial Sloan Kettering Cancer Center, New York, New York.,Weill Cornell Medical College, New York, New York
| | - David S Klimstra
- Memorial Sloan Kettering Cancer Center, New York, New York.,Weill Cornell Medical College, New York, New York
| | - Leonard B Saltz
- Memorial Sloan Kettering Cancer Center, New York, New York.,Weill Cornell Medical College, New York, New York
| | - Ghassan K Abou-Alfa
- Memorial Sloan Kettering Cancer Center, New York, New York. .,Weill Cornell Medical College, New York, New York
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Usón Junior PLS, Rother ET, Maluf FC, Bugano DDG. Meta-analysis of Modified FOLFIRINOX Regimens for Patients With Metastatic Pancreatic Cancer. Clin Colorectal Cancer 2018; 17:187-197. [PMID: 29615310 DOI: 10.1016/j.clcc.2018.03.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Revised: 03/07/2018] [Accepted: 03/08/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND We performed a meta-analysis of previous reports evaluating the effect of mFIO (modified FOLFIRINOX; leucovorin, 5-fluorouracil, irinotecan, oxaliplatin) regimens in advanced pancreatic cancer. MATERIALS AND METHODS We performed a meta-analysis of reported studies in PubMed, Scopus, and Web of Science (1950-2016) in December 2016. The inclusion criteria were randomized trials, prospective or retrospective cohorts, patients with metastatic pancreatic adenocarcinoma, the use of mFIO or FOLFIRINOX (FIO) chemotherapy, and available information for ≥ 1 efficacy endpoint (response rate, progression-free survival, and/or overall survival). The outcomes were compared according to the chemotherapy regimen using a random effects model. We also performed a meta-regression analysis to evaluate the effect of dose reductions on outcomes. RESULTS Of 2525 abstracts, 32 were considered eligible. Modifications in the FIO regimen included omission of the 5-fluorouracil bolus and/or dose reductions in infusional 5-fluorouracil, irinotecan, and/or oxaliplatin. mFIO was not associated with inferior response rates (32% vs. 33%; P = .879), lower rates of survival at 11 months (47% vs. 50%; P = .38), or lower 6-month progression-free survival rates (47% vs. 53%; P = .38). The meta-regression of the percentage of dose reduction failed to show any association. CONCLUSION The results of the present meta-analysis with a combined sample size of 1461 patients suggest that it is reasonable to consider mFIO regimens for patients with metastatic pancreatic adenocarcinoma.
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Enzler T, Bates S. Clinical Trials in Pancreatic Cancer: A Long Slog. Oncologist 2017; 22:1424-1426. [PMID: 28982802 PMCID: PMC5728038 DOI: 10.1634/theoncologist.2017-0453] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Accepted: 09/07/2017] [Indexed: 12/27/2022] Open
Abstract
Many investigators have turned their efforts toward improving the gemcitabine/nab‐paclitaxel combination by the addition of a third agent. This commentary highlights efforts to date, including the Clinical Trial Results by Ko et al.: A Randomized Double‐Blinded Phase II Trial of Gemcitabine and Nab‐Paclitaxel Plus Apatorsen or Placebo in Patients with Metastati Pancreatic Cancer: The RAINIER Trial.
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Affiliation(s)
- Thomas Enzler
- Division of Hematology and Oncology, Department of Medicine, Columbia University Medical Center, New York, New York, USA
| | - Susan Bates
- Division of Hematology and Oncology, Department of Medicine, Columbia University Medical Center, New York, New York, USA
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Cross-over comparison and new chemotherapy regimens in metastatic pancreatic cancer. MEMO-MAGAZINE OF EUROPEAN MEDICAL ONCOLOGY 2017; 10:136-140. [PMID: 28989542 PMCID: PMC5605578 DOI: 10.1007/s12254-017-0352-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Accepted: 08/10/2017] [Indexed: 12/17/2022]
Abstract
Despite decades of research, pancreatic ductal adenocarcinoma (PDAC) is still one of the most lethal malignant diseases with a devastating 5‑year overall survival of only 4–5%. Indeed, long-term survival was not affected by the introduction of new systemic cytotoxic chemotherapies which remain the key cornerstone in the treatment of metastatic PDAC. In the first-line setting, FOLFIRINOX based upon the results of the PRODIGE/ACCORD trial and gemcitabine with albumin-bound paclitaxel (GNP) based upon the MPACT trial have both been approved as therapeutic options for patients with no significant comorbidities and good performance status. As there is no direct comparison between these regimens, the choice in first-line treatment depends on the toxicity profile, patient’s preferences and reimbursability. In the second-line setting, the results of the NAPOLI-1 trial have led to the approval of nanoliposomal irinotecan (nal-iri) in combination with 5‑fluorouracil (5-FU) for the treatment of patients with mPDAC progressing under gemcitabine-based chemotherapy and therefore this regimen is the first to be approved for use in second-line therapy.
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Lambert A, Gavoille C, Conroy T. Current status on the place of FOLFIRINOX in metastatic pancreatic cancer and future directions. Therap Adv Gastroenterol 2017; 10:631-645. [PMID: 28835777 PMCID: PMC5557187 DOI: 10.1177/1756283x17713879] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Accepted: 05/09/2017] [Indexed: 02/04/2023] Open
Abstract
Pancreatic cancer (PC) incidence rates are rapidly increasing in developed countries, with half the patients being metastatic at diagnosis. For decades, fluorouracil, then gemcitabine regimens were the preferred palliative first-line options for fit patients with metastatic PC. FOLFIRINOX (a combination of bolus and infusional fluorouracil, leucovorin, irinotecan and oxaliplatin) was introduced to clinical practice in 2010 due to the results of the phase II/III trial (PRODIGE 4/ACCORD 11) comparing FOLFIRINOX with single-agent gemcitabine as first-line treatment for patients with MPC. Median overall survival, progression-free survival, and objective response rate were superior with FOLFIRINOX over gemcitabine and there was prolonged time to definitive deterioration in quality of life. Although FOLFIRINOX was also associated with increased toxicity, mainly febrile neutropenia and diarrhea, there has been rapid uptake of this regimen. This review closely examines optimal management and prevention of toxicities, international recommendations for first-line treatment, and use of modified FOLFIRINOX protocols. In this review, we also look at the potential benefit of FOLFIRINOX in selected groups of patients: second-line therapy, adjuvant chemotherapy, induction therapy in patients with borderline resectable and locally advanced PC. Robust validation of the FOLFIRINOX regimen in these settings requires confirmation in further randomized trials.
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Affiliation(s)
- Aurélien Lambert
- Department of Medical Oncology, Institut de Cancérologie de Lorraine, Vandœuvre-lès-Nancy, France
| | - Céline Gavoille
- Department of Medical Oncology, Institut de Cancérologie de Lorraine, Vandœuvre-lès-Nancy, France
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31
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Alistar A, Morris BB, Desnoyer R, Klepin HD, Hosseinzadeh K, Clark C, Cameron A, Leyendecker J, D'Agostino R, Topaloglu U, Boteju LW, Boteju AR, Shorr R, Zachar Z, Bingham PM, Ahmed T, Crane S, Shah R, Migliano JJ, Pardee TS, Miller L, Hawkins G, Jin G, Zhang W, Pasche B. Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single-centre, open-label, dose-escalation, phase 1 trial. Lancet Oncol 2017; 18:770-778. [PMID: 28495639 PMCID: PMC5635818 DOI: 10.1016/s1470-2045(17)30314-5] [Citation(s) in RCA: 175] [Impact Index Per Article: 21.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Revised: 02/24/2017] [Accepted: 02/27/2017] [Indexed: 12/24/2022]
Abstract
Background Pancreatic cancer statistics are dismal, with a five-year survival of less than 10%, and over 50% of patients presenting with metastatic disease. Metabolic reprogramming is an emerging hallmark of pancreatic adenocarcinoma, including aerobic glycolysis, oxidative phosphorylation, glutaminolysis, lipogenesis and lipolysis, autophagic status, and anti-oxidative stress. CPI-613 is a novel anti-cancer agent that selectively targets the altered form of mitochondrial energy metabolism in tumor cells, causing changes in mitochondrial enzyme activities and redox status which lead to apoptosis, necrosis and autophagy of tumor cells. Methods This is a phase 1 study to determine the maximum-tolerated dose (MTD) of CPI-613 when used in combination with modified FOLFIRINOX (oxaliplatin at 65 mg/m2 and irinotecan at 140 mg/m2, and fluorouracil 400 mg/m2 bolus and 2400 mg/m2 over 46 h) in combination with CPI-613 in patients with newly diagnosed metastatic pancreatic adenocarcinoma with good bone marrow, liver and kidney function and good performance status (NCT01835041 – closed to recruitment). A two-stage dose-escalation scheme (single patient and traditional 3+3 design) was applied. In the single patient stage, one patient was accrued per dose level. The starting dose of CPI-613 was 500 mg/m2/day; the dose level was then escalated by doubling the previous dose if there was no toxicity greater than Grade 2 within 4 weeks attributed as probably or definitely related to CPI-613. The traditional 3+3 dose-escalation stage was triggered if toxicity attributed as probably or definitely related to CPI-613 was ≥ Grade 2. The dose level for CPI-613 for the first cohort in the traditional dose-escalation stage was the same as used in the last cohort of the single patient dose-escalation stage. Secondary objectives were safety, preliminary efficacy, and tissue collection for future analyses. Response rates, progression-free survival and overall survival data were assessed in the patients treated at the MTD. Findings Twenty patients were enrolled April 22, 2013 – January 8, 2016. The MTD of CPI-613 was 500 mg/m2. The median number of treatment cycles administered at the MTD was 11 (interquartile range, 4–19). Two patients enrolled at a higher dose (1000 mg/m2) both experienced a DLT (dose limiting toxicity). There were 2 unexpected serious adverse events (SAEs), both for the first patient enrolled: 1) possible leaching due to infusion of CPI-613 via non-PVC tubing, and 2) the patient re- accessed her port at home after accidental de-access. Neither incident resulted in a negative clinical outcome. Expected SAEs were: thrombocytopenia, anemia and lymphopenia (all for Patient #2, with anemia and lymphopenia being a DLT); hyperglycemia (Patient #7); hypokalemia, hypoalbuminemia and sepsis (Patient #11); and neutropenia (Patient #20). There was no grade 5 toxicity. For the 18 patients treated at the MTD, the most common Grade 3–4 toxicities were hypokalemia (6/18, 33%), diarrhea (5/18, 28%) and abdominal pain (4/18, 22%). Sensorial neuropathy (17/18, 94%) was managed with dose de-escalation or discontinuation per standard of care. None of the patients experienced grade 4 or 5 neuropathy. No patients died while on active treatment; 11 study participants died, with cause of death as terminal pancreatic cancer. Among the 18 patients treated with the MTD, there were 3 patients with a complete response (CR), 1 with a non-CR/non-progressive disease, 7 with a partial response (PR), 3 with stable disease, and 4 with PD. The partial + complete response rate was 61% (11/18). Interpretation The treatment was well tolerated and all end points were met. The intriguing signal of efficacy will require validation in a phase 2 study. Funding Comprehensive Cancer Center of Wake Forest Baptist Medical Center
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Affiliation(s)
- Angela Alistar
- Section on Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
| | - Bonny B Morris
- Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Rodwige Desnoyer
- Section on Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Heidi D Klepin
- Section on Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Keyanoosh Hosseinzadeh
- Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Clancy Clark
- Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Section on Surgical Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Amy Cameron
- Section on Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - John Leyendecker
- UT Southwestern Medical Center, Department of Radiology, Dallas, TX, USA
| | - Ralph D'Agostino
- Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Biostatistics, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Umit Topaloglu
- Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Lakmal W Boteju
- Department of Chemistry, Cornerstone Pharmaceuticals, Cranbury, NJ, USA
| | - Asela R Boteju
- Department of Chemistry, Cornerstone Pharmaceuticals, Cranbury, NJ, USA
| | - Rob Shorr
- Department of Chemistry, Cornerstone Pharmaceuticals, Cranbury, NJ, USA
| | - Zuzana Zachar
- Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, USA
| | - Paul M Bingham
- Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, USA
| | - Tamjeed Ahmed
- Section on Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Sandrine Crane
- Section on Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Riddhishkumar Shah
- Section on Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - John J Migliano
- Section on Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Timothy S Pardee
- Section on Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Lance Miller
- Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Gregory Hawkins
- Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Guangxu Jin
- Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Wei Zhang
- Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Boris Pasche
- Section on Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
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Kobayashi N, Shimamura T, Tokuhisa M, Goto A, Endo I, Ichikawa Y. Effect of FOLFIRINOX as second-line chemotherapy for metastatic pancreatic cancer after gemcitabine-based chemotherapy failure. Medicine (Baltimore) 2017; 96:e6769. [PMID: 28489753 PMCID: PMC5428587 DOI: 10.1097/md.0000000000006769] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Revised: 04/03/2017] [Accepted: 04/06/2017] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND This study aimed to determine the maximum tolerated dose (MTD), dose-limiting toxicity, and efficacy of second-line chemotherapy with FOLFIRINOX after gemcitabine (GEM)-based chemotherapy failure in metastatic pancreatic cancer (MPC). METHODS We studied 18 histopathologically proven MPC patients. The schedule was 85 mg/m oxaliplatin, irinotecan, and 400 mg/m leucovorin, followed by 400 mg/m 5-fluorouracil (5-FU) as a bolus on day 1 and 2400 mg/m 5-FU as a 46-hour continuous infusion biweekly. The dose of irinotecan was defined as follows: level 0: 100 mg/m, level 1: 125 mg/m, level 2: 150 mg/m, and level 3: 180 mg/m. The doses of other drugs were fixed. The primary endpoint of phase II study was the response rate (RR). RESULTS We initially evaluated 6 patients in a phase I study. One patient developed neutropenia and 1 patient developed hyperglycemia and severe infection. Accordingly, level 1 was chosen as the MTD. According to a phase II study, the RR was 22.2% and the disease control rate was 61.1%. The progression-free survival and overall survival were 2.8 (range, 0.7-19.1) and 9.8 (2.4-19.8) months, respectively. The most common severe adverse event was neutropenia (66.7%). Febrile neutropenia occurred in 1 (5.6%) case. CONCLUSION The recommended dose was 85 mg/m oxaliplatin, 100 mg/m irinotecan, and 400 mg/m leucovorin, followed by 400 mg/m 5-FU as a bolus on day 1 and 2400 mg/m 5-FU as a 46-hour continuous infusion. These results indicate that second-line FOLFIRINOX is a marginally effective treatment for GEM-based chemotherapy failure cases.
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Affiliation(s)
- Noritoshi Kobayashi
- Graduate School of Medicine, Department of Oncology, Yokohama City University, Japan Shimamura Clinic and Yokohama City University Graduate School of Medicine Department of Oncology Graduate School of Medicine, Department of Gastroenterological Surgery, Yokohama City University, Japan
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Maebayashi T, Ishibashi N, Aizawa T, Sakaguchi M, Sato T, Kawamori J, Tanaka Y. Treatment outcomes of concurrent hyperthermia and chemoradiotherapy for pancreatic cancer: Insights into the significance of hyperthermia treatment. Oncol Lett 2017; 13:4959-4964. [PMID: 28588736 DOI: 10.3892/ol.2017.6066] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Accepted: 04/05/2017] [Indexed: 12/18/2022] Open
Abstract
Patients with locally advanced unresectable pancreatic cancer (LAUPC) have a poor prognosis. In addition their quality of life impaired by cancer pain and biliary tract infections. Therefore, multimodality therapy and selection of optimal treatment methods are essential for achieving prolonged survival. The present study investigated the significance of using hyperthermia concurrently with multimodality therapy to improve treatment outcomes in patients with LAUPC. In total, 13 patients receiving concurrent hyperthermia and chemoradiotherapy (HCR) or chemoradiotherapy (CR) alone for LAUPC between 2002 and 2013 were analyzed retrospectively. Of the 13 patients, 5 received concurrent HCR and 8 received CR. The chemotherapy regimens were 5-fluorouracil (5-FU) in 5 patients and gemcitabine hydrochloride (GEM) in the other 8. Patients who gave consent for hyperthermia treatment received GEM plus CR. The median overall survival period for all patients was 12 months and the 1-year survival rate was 55%; the corresponding values were 12 months and 57% in the GEM CR group, and 15 months and 80% in the HCR group. Univariate analyses was perfomed to identify factors predicting recurrence after treatment. The potential prognostic factors analyzed were: Age, sex, performance status, location, tumor size, the tumor marker CA 19-9, total radiation dose, chemotherapy and hyperthermia. Univariate analysis for factors associated with outcomes revealed a significant difference favoring the HCR group [relative risk=15.97 (95% confidence interval: 12.87-19.83) P=0.021]. In conclusion, hyperthermia merits active recommendation to pancreatic cancer patients who have a positive attitude toward this treatment and whose performance status is satisfactory.
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Affiliation(s)
- Toshiya Maebayashi
- Department of Radiology, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Naoya Ishibashi
- Department of Radiology, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Takuya Aizawa
- Department of Radiology, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Masakuni Sakaguchi
- Department of Radiology, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Tsutomu Sato
- Radiology Clinic, Sonoda Medical Corporations, Adachi-ku, Tokyo 121-0064, Japan
| | - Jiro Kawamori
- Department of Radiation Oncology, St. Luke's International Hospital, Chuo-ku, Tokyo 104-8560, Japan
| | - Yoshiaki Tanaka
- Department of Radiation Oncology, Kawasaki Saiwai Hospital, Kawasaki, Kanagawa 212-0014, Japan
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Lee JC, Kim JW, Ahn S, Kim HW, Lee J, Kim YH, Paik KH, Kim J, Hwang JH. Optimal dose reduction of FOLFIRINOX for preserving tumour response in advanced pancreatic cancer: Using cumulative relative dose intensity. Eur J Cancer 2017; 76:125-133. [PMID: 28324747 DOI: 10.1016/j.ejca.2017.02.010] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Revised: 01/26/2017] [Accepted: 02/07/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND FOLFIRINOX has increased efficacy but also toxicity. Despite various modified FOLFIRINOX regimens, how much reduction is acceptable remains unclear. This study aimed to find the optimal relative dose intensity (RDI, %) of FOLFIRINOX that preserves tumour responses in patients with advanced pancreatic cancer (PC). METHODS We reviewed 201 patients with PC treated with first-line FOLFIRINOX during 2012-2015. We established a modified Hryniuk model (http://www.rdicalc.com) and defined cumulative RDI (cRDI, %). The optimal cRDI thresholds for response rate (RR) and disease control rate (DCR) were assessed using receiver operating characteristic (ROC) analysis. Relationships between cRDI and haematologic toxicities (neutropenia and febrile neutropenia [FN]) were also analysed according to use of granulocyte colony-stimulating factor (G-CSF). RESULTS Among 156 eligible patients, 133 (48 locally advanced PC and 85 metastatic PC) completed initial treatment plan prior to the first radiological evaluation (median 58 days; 71.8% cRDI). For optimal cRDI thresholds, ROC curves showed a 71.2% cRDI for RR (83.3% sensitivity, 64.7% specificity, and 0.746 area under the curve [AUC]) and a 55.3% cRDI for DCR (93.6% sensitivity, 62.5% specificity and 0.805 AUC). Among 96 patients who did not receive prophylactic G-CSF, cRDI ≥80.1% was a significant predictor for frequent FN (73.7% sensitivity, 72.7% specificity and 0.793 AUC). There was no correlation between cRDI and haematologic toxicities in patients receiving prophylactic G-CSF. CONCLUSION To preserve optimal RR and DCR in advanced PC, cRDI values for FOLFIRINOX >70% and >55%, respectively, are recommended. If cRDI is >80%, primary G-CSF prophylaxis is needed.
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Affiliation(s)
- Jong-Chan Lee
- Division of Gastroenterology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Jin Won Kim
- Division of Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Soyeon Ahn
- Department of Biostatistics, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Hyoung Woo Kim
- Division of Gastroenterology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Jongchan Lee
- Division of Gastroenterology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Young Hoon Kim
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Kyu-Hyun Paik
- Department of Internal Medicine, Eulgi University College of Medicine, Daejeon, Republic of Korea
| | - Jaihwan Kim
- Division of Gastroenterology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Jin-Hyeok Hwang
- Division of Gastroenterology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
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Varghese AM, Lowery MA, Yu KH, O'Reilly EM. Current management and future directions in metastatic pancreatic adenocarcinoma. Cancer 2016; 122:3765-3775. [PMID: 27649047 PMCID: PMC5565512 DOI: 10.1002/cncr.30342] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Revised: 06/28/2016] [Accepted: 07/25/2016] [Indexed: 02/06/2023]
Abstract
Of the anticipated 50,000 individuals expected to be diagnosed with pancreatic cancer in 2016, the majority will have metastatic disease. Given the noncurative nature of advanced pancreatic adenocarcinoma, treatment is aimed at inducing disease regression, controlling symptom, and extending life. The last 5 years have been marked by advances in the treatment of metastatic pancreatic cancer, specifically the approval by the US Food and Drug Administration of 2 combination chemotherapy regimens and the widespread use of a third, which have reproducibly been shown to improve survival. Ongoing studies are building on these regimens along with targeted and immunotherapeutic agents. This article will review the current treatment standards and emerging targets for metastatic pancreatic cancer. Cancer 2016;122:3765-3775. © 2016 American Cancer Society.
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Affiliation(s)
- Anna M Varghese
- Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Maeve A Lowery
- Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Kenneth H Yu
- Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Eileen M O'Reilly
- Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
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Ghosn M, Ibrahim T, Assi T, El Rassy E, Kourie HR, Kattan J. Dilemma of first line regimens in metastatic pancreatic adenocarcinoma. World J Gastroenterol 2016; 22:10124-10130. [PMID: 28028360 PMCID: PMC5155171 DOI: 10.3748/wjg.v22.i46.10124] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2016] [Revised: 09/23/2016] [Accepted: 10/31/2016] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is one of the deadliest cancers, ranking fourth among cancer-related deaths. Despite all the major molecular advances and treatment breakthroughs, mainly targeted therapies, the cornerstone treatment of metastatic pancreatic cancer (mPC) remains cytotoxic chemotherapy. In 2016, more than 40 years after the introduction of gemcitabine in the management of mPC, the best choice for first-line treatment has not yet been fully elucidated. Two main strategies have been adopted to enhance treatment efficacy. The first strategy is based on combining non-cross resistant drugs, while the second option includes the development of newer generations of chemotherapy. More recently, two new regimens, FOLFIRINOX and gemcitabine/nab-paclitaxel (GNP), have both been shown to improve overall survival in comparison with gemcitabine alone, at the cost of increased toxicity. Therefore, the best choice for first line therapy is a matter of debate. For some authors, FOLFIRINOX should be the first choice in patients with an Eastern Cooperative Oncology Group score (0-1) given its lower hazard ratio. However, others do not share this opinion. In this paper, we review the main comparison points between FOLFIRINOX and GNP. We analyze the two pivotal trials to determine the similarities and differences in study design. In addition, we compare the toxicity profile of the two regimens as well as the impact on quality of life. Finally, we present studies revealing real life experiences and review the advantages and disadvantages of possible second-line therapies including their cost effectiveness.
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Gostimir M, Bennett S, Moyana T, Sekhon H, Martel G. Complete pathological response following neoadjuvant FOLFIRINOX in borderline resectable pancreatic cancer - a case report and review. BMC Cancer 2016; 16:786. [PMID: 27724927 PMCID: PMC5057443 DOI: 10.1186/s12885-016-2821-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Accepted: 09/29/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Pancreatic cancer is among the top 5 most common cancers worldwide, but is particularly devastating due to its insidious nature. Complete surgical resection remains the only potential curative treatment, although only 20 % of patients present with a resectable tumor. Patients may alternatively present with borderline resectable pancreatic cancer or locally advanced pancreatic cancer and can be offered treatment with neoadjuvant intent. The effectiveness of these treatments is unclear and there is a paucity of data to suggest one optimal treatment approach. CASE PRESENTATION We describe a 61-year-old female who presented with a two-week history of obstructive jaundice in the context of vague abdominal pain that had been ongoing for years prior to her visit. CT scan of the abdomen confirmed a hypovascular mass in the uncinate process consistent with borderline resectable pancreatic cancer. Pancreatic adenocarcinoma was confirmed with endoscopic ultrasound guided fine-needle aspiration cytology. Following multidisciplinary discussion, it was recommended that she undergo treatment with FOLFIRINOX. After a total of 13 cycles, follow up CT revealed that the lesion had decreased in size and she was offered resection as a potentially curative treatment. She underwent pancreaticoduodenectomy. Final pathology report revealed no evidence of residual adenocarcinoma (ypT0 ypN0 (0/23)). The patient remains disease-free 15 months following surgery. CONCLUSION To date, there have been very few reports of a complete pathological response following neoadjuvant therapy in borderline resectable or locally advanced pancreatic cancer. This report describes a unique case of a complete pathological remission in a patient with borderline resectable pancreatic cancer following FOLFIRINOX therapy alone and adds to the growing base of evidence meriting the initiation of clinical trials to assess the efficacy of FOLFIRINOX in these subsets of pancreatic cancer.
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Affiliation(s)
- Mišo Gostimir
- Faculty of Medicine, University of Ottawa, 451 Smyth Rd, K1H 8 M5 Ottawa, Canada
| | - Sean Bennett
- Department of Surgery, Division of General Surgery, University of Ottawa, 451 Smyth Rd, K1H 8 M5 Ottawa, Canada
| | - Terence Moyana
- Department of Pathology and Laboratory Medicine, University of Ottawa, 501 Smyth Rd, K1H 8 L6 Ottawa, Canada
| | - Harman Sekhon
- Department of Pathology and Laboratory Medicine, University of Ottawa, 501 Smyth Rd, K1H 8 L6 Ottawa, Canada
| | - Guillaume Martel
- Department of Surgery, Liver and Pancreas Unit, University of Ottawa, 501 Smyth Rd, K1H 8 L6 Ottawa, Canada
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Westphalen CB, Kruger S, Haas M, Heinemann V, Boeck S. Safety of palliative chemotherapy in advanced pancreatic cancer. Expert Opin Drug Saf 2016; 15:947-54. [PMID: 27070177 DOI: 10.1080/14740338.2016.1177510] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Pancreatic cancer is a major health burden. Currently, the majority of patients is diagnosed at advanced stages and thus qualifies for palliative chemotherapy. Gemcitabine monotherapy has been the gold standard for many years. Recently, more effective chemotherapeutic regimens have shown meaningful clinical activity in patients with metastatic pancreatic cancer. AREAS COVERED In this review we have aimed to give an overview on the treatment options for patients diagnosed with metastatic pancreatic cancer with an emphasis on the safety and toxicity of the applied regimens. We have conducted a pubmed search using the terms 'metastatic pancreatic cancer', 'palliative chemotherapy', 'safety' and 'toxicity'. Our special focus rested on randomized phase III trials to provide readers with the highest level of available evidence. EXPERT OPINION The emergence of new and more effective chemotherapy regimens gives clinicians more freedom in the treatment of metastatic pancreatic cancer. While being more effective, these regiments have a considerable degree of toxicity. Choosing the right treatment for any individual will be the next major challenge treating patients with pancreatic cancer.
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Affiliation(s)
- C Benedikt Westphalen
- a Department of Internal Medicine III and Comprehensive Cancer Center , Klinikum Grosshadern, Ludwig-Maximilians-University of Munich , Munich , Germany
| | - Stephan Kruger
- a Department of Internal Medicine III and Comprehensive Cancer Center , Klinikum Grosshadern, Ludwig-Maximilians-University of Munich , Munich , Germany
| | - Michael Haas
- a Department of Internal Medicine III and Comprehensive Cancer Center , Klinikum Grosshadern, Ludwig-Maximilians-University of Munich , Munich , Germany
| | - Volker Heinemann
- a Department of Internal Medicine III and Comprehensive Cancer Center , Klinikum Grosshadern, Ludwig-Maximilians-University of Munich , Munich , Germany
| | - Stefan Boeck
- a Department of Internal Medicine III and Comprehensive Cancer Center , Klinikum Grosshadern, Ludwig-Maximilians-University of Munich , Munich , Germany
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