|
1
|
Zhang S, Yang J, Zhan H, Yang B, Rong P, Luo Y, Shi C, Chen Y, Yang J. Incidence and non-genetic risk factors of irinotecan-induced severe neutropenia in Chinese adult inpatients. Medicine (Baltimore) 2023; 102:e33005. [PMID: 36862924 PMCID: PMC9981354 DOI: 10.1097/md.0000000000033005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/04/2023] Open
Abstract
To analyze the incidence and nongenetic risk factors of irinotecan-induced severe neutropenia in the hospital, and provide additional reference and help for clinical treatment. A retrospective analysis of patients who received irinotecan based chemotherapy from May 2014 to May 2019 in Renmin Hospital of Wuhan University was conducted. Univariate analysis and binary logistic regression analysis with the forward stepwise method were used to assess the risk factors associated with severe neutropenia induced by irinotecan. Of the 1312 patients treated with irinotecan-based regmines, only 612 patients met the inclusion criteria, and 32 patients developed irinotecan-induced severe neutropenia. In the univariate analysis, variables associated with severe neutropenia were tumor type, tumor stage, and therapeutic regimen. In the multivariate analysis, irinotecan plus lobaplatin, lung cancer or ovarian cancer, tumor stage T2, T3, and T4, were identified as risk factors that contributed independently to irinotecan-induced severe neutropenia (P < .05), respectively. The results showed that the incidence of irinotecan-induced severe neutropenia was 5.23% in the hospital. The risk factors included tumor type (lung cancer or ovarian cancer), tumor stage (T2, T3, and T4) and therapeutic regimen (irinotecan plus lobaplatin). Therefore, for patients with these risk factors, it might be advisable to actively consider optimum management to reduce the occurrence of irinotecan-induced severe neutropenia.
Collapse
Affiliation(s)
- Shuxiao Zhang
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
| | - JingXiang Yang
- Department of Pharmacy, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Haiyan Zhan
- Department of Pharmacy, Wuhan Jinyintan Hospital, Wuhan, China
| | - Boning Yang
- Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - PeiPei Rong
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yi Luo
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
| | - Cai Shi
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
| | - Ying Chen
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
| | - Jian Yang
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
- * Correspondence: Jian Yang, Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, China (e-mail: )
| |
Collapse
|
|
2
|
Correa E, Lindsay T, Dotan E. Management of Metastatic Colorectal Carcinoma in Older Adults: Balancing Risks and Benefits of Novel Therapies. Drugs Aging 2021; 38:639-654. [PMID: 34143421 PMCID: PMC9951235 DOI: 10.1007/s40266-021-00869-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/22/2021] [Indexed: 11/25/2022]
Abstract
The prevalence of older patients with metastatic colorectal cancer (mCRC) will continue to increase with our aging population. Treatment of mCRC has changed significantly in the last few decades as we have learned how to personalize the treatment of mCRC to the biology of the tumor, utilizing new treatment approaches. With an ever-changing treatment paradigm, managing the population of older adults becomes paramount. This review highlights the pivotal clinical trials that defined the use of systemic therapy, immunotherapy and targeted therapies for mCRC, and how those are applied to the older patient population. In addition, we outline the tools for an in-depth assessment of an older adult in regards to treatment planning and management of therapy-related toxicities. A comprehensive geriatric assessment can assist in the selection of treatment for an older adult with mCRC. While frail older patients can frequently only tolerate single agents or modified regimens, fit older adults remain candidates for a wider range of treatment options. However, since all of these treatments are associated with possible toxicities, each patient's treatment must be personalized to the patient's goals and wishes through a shared decision-making process.
Collapse
Affiliation(s)
- Erika Correa
- Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Timothy Lindsay
- Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Efrat Dotan
- Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
| |
Collapse
|
|
3
|
Aparicio T, Canouï-Poitrine F, Caillet P, François E, Cudennec T, Carola E, Albrand G, Bouvier AM, Petri C, Couturier B, Phelip JM, Bengrine-Lefevre L, Paillaud E. Treatment guidelines of metastatic colorectal cancer in older patients from the French Society of Geriatric Oncology (SoFOG). Dig Liver Dis 2020; 52:493-505. [PMID: 32029404 DOI: 10.1016/j.dld.2019.12.145] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 12/21/2019] [Accepted: 12/23/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Several guidelines dedicated to metastatic colorectal cancer (mCRC) are available. Since 2013 no recent guidelines are specifically dedicated to older patients and based on a systematic review. MATERIALS AND METHODS A multidisciplinary Task Force with digestive oncologists, geriatricians and methodologists from the SoFOG was formed in 2016 to update recommendations on medical treatment of mCRC based on a systematic review of publications from 2000 to 2018. Search strategy has followed a standardized protocol from the formulation of clinical questions and definition of a search algorithm to the selection of complete articles for recommendations. RESULTS The four selected key questions were: For which older patients with mCRC can we considered: (1) Any chemotherapy, (2) Mono or poly-chemotherapy, (3) Anti-angiogenic therapy, (4) Other targeted therapy. Main recommendations for older patients are: (1) Omission of chemotherapy should be discussed with a geriatrician for patients with severe comorbidities, advanced dementia, uncontrolled psychiatric disorder or severe loss of autonomy. (2) If tumor response is not the main aim, a mono-chemotherapy with 5-fluorouracil combined with bevacizumab is recommended as first-line. (3) For patients with symptoms related to metastases or with a planned metastasis ablation, a doublet chemotherapy combined with bevacizumab or anti-EGFR antibody in the context of a RAS wild type tumor is recommended as first-line. Preliminary data suggest that regorafenib may be used, in its registered indication, in patients under 80 with a performance status of 0 and no autonomy alterations and that trifluridine-tipiracil may be used with a tight supervising of hematological function.
Collapse
Affiliation(s)
- Thomas Aparicio
- Department of Gastroenterology and Digestive Oncology, Saint Louis Hospital, AP-HP, University of Paris, Paris, France.
| | - Florence Canouï-Poitrine
- Clinical Epidemiology and Ageing Unit, Henri Mondor Hospital, APHP, EA 7376, CEpiA- IMRB, University of Paris-Est, Créteil, France
| | - Philippe Caillet
- Department of Geriatry, Georges Pompidou Hospital, APHP, University of Paris, Paris, France
| | - Eric François
- Department of Medical Oncology, Antoine-Lacassagne Center, University Côte d'Azur, Nice, France
| | - Tristan Cudennec
- Department of Geriatry, Ambroise Paré Hospital, APHP, University Versailles - Saint Quentin, Boulogne-Billancourt, France
| | - Elisabeth Carola
- Department of Medical Oncology, Public Sud de l'Oise Hospital, Creil, France
| | - Gilles Albrand
- Department of Geriatry, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre Bénite, France
| | - Anne-Marie Bouvier
- Digestive Cancer Registry of Burgundy, INSERM UMR1231 EPICAD University of Burgundy Franche Comté, Dijon, France
| | - Camille Petri
- Clinical Epidemiology and Ageing Unit, Henri Mondor Hospital, APHP, EA 7376, CEpiA- IMRB, University of Paris-Est, Créteil, France
| | - Bérengère Couturier
- Clinical Epidemiology and Ageing Unit, Henri Mondor Hospital, APHP, EA 7376, CEpiA- IMRB, University of Paris-Est, Créteil, France
| | - Jean-Marc Phelip
- Department of Gastroenterology and Digestive Oncology, Saint-Etienne Hospital, University Jean Monnet, Saint-Priest-en-Jarez, France
| | | | - Elena Paillaud
- Department of Geriatry, Georges Pompidou Hospital, APHP, University of Paris, Paris, France
| |
Collapse
|
|
4
|
Leslom AN, Alqahtani FJ, Hanash AAS, Alsubaie AA, Alamri MS. Treatment response in elderly patients with advanced colorectal cancer at King Abdulaziz Medical City, Princess Norah Oncology Center, Jeddah. J Family Med Prim Care 2020; 9:898-903. [PMID: 32318442 PMCID: PMC7114059 DOI: 10.4103/jfmpc.jfmpc_993_19] [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] [Received: 09/11/2019] [Revised: 01/23/2020] [Accepted: 02/03/2020] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION Colorectal carcinoma is the most evident carcinoma in the elderly. Despite its high incidence and mortality rate, there is insufficient research about the best treatment options for colorectal carcinoma. OBJECTIVE This study was designed to assess the best treatment modality for colorectal carcinoma in elderly Saudi patients. METHODS We conducted a retrospective analysis of medical records at the Princess Norah Oncology Center (PNOC), King Abdulaziz Medical City, Jeddah, Saudi Arabia. We included patients treated at PNOC between 2010 and 2015. Only patients aged above 70 years with advanced colon were included in the study. RESULTS The cohort included 57 patients with an average age of 76.51 with 27 alive patients and 30 dead patients. Nonmucinous adenocarcinoma had significant higher mortality (n = 20). Most patients received surgical treatment which was associated with less risk for mortality; however, it was nonsignificant. Surgery was followed by first-line treatment which had a mortality rate of 50%. The least treatment associated with mortality was local liver treatment (n = 0). Survival analysis found that only treatment with significant higher survival was shift to next line of treatment (at least once) [HR = 0.06, 95% CI (0.00, 0.79), P value = 0.03]. Other treatments were not associated with significant mortality reduction. First-line treatment was associated with higher mortality risk; nevertheless, it was nonsignificant. CONCLUSION Local radiotherapy and local liver ablation had the least mortality rate. However, in multivariate Cox regression analysis, we found that shift to next line of treatment was associated with the significant high survival rate.
Collapse
|
|
5
|
Yu IS, Cheung WY. Metastatic Colorectal Cancer in the Era of Personalized Medicine: A More Tailored Approach to Systemic Therapy. Can J Gastroenterol Hepatol 2018; 2018:9450754. [PMID: 30519549 PMCID: PMC6241232 DOI: 10.1155/2018/9450754] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2018] [Accepted: 10/30/2018] [Indexed: 12/21/2022] Open
Abstract
Colorectal cancer is the second most common malignancy diagnosed in Canada. Despite declining incidence and mortality rates in recent years, there is still a significant number of cases that are metastatic at presentation. Fluoropyrimidine-based chemotherapy was the backbone of colorectal cancer treatment, but the addition of irinotecan and oxaliplatin to form combination regimens has significantly improved overall survival. In the past decade, the development of novel biologic agents including therapies directed against vascular endothelial growth factor and epidermal growth factor receptor has further altered the landscape of metastatic colorectal cancer treatment. However, clinical trials have demonstrated that not all patients respond to these therapies similarly and consideration must be given to individual patient- and tumor-related factors. A more tailored and biomarker driven approach to treatment selection can optimize outcomes and avoid unnecessary adverse effects. In this review article, we offer a comprehensive overview of the panel of clinical- and tumor-associated characteristics that influence treatment decisions in metastatic colorectal cancer and how this sets the foundation for a more personalized treatment strategy in oncology.
Collapse
Affiliation(s)
- Irene S. Yu
- University of British Columbia, Vancouver, Canada
| | | |
Collapse
|
|
6
|
Wedding U, Honecker F, Bokemeyer C, Pientka L, Höffken K. Tolerance to Chemotherapy in Elderly Patients with Cancer. Cancer Control 2017; 14:44-56. [PMID: 17242670 DOI: 10.1177/107327480701400106] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Background Due to demographic changes, the number of elderly people with cancer will increase in the next decades. In the past, elderly patients with cancer were often excluded from clinical trials. Chronological age has been considered a risk factor for increased toxicity and reduced tolerance to chemotherapy. Methods We present a review on toxicity of chemotherapy and factors associated with toxicity in elderly patients with cancer, and we discuss chemotherapeutic agents and treatment options in treating this patient population. Results Age is a risk factor for increased toxicity to chemotherapy and decreased tolerance. However, few trials have been reported with adjustment for age-associated changes such as impairment of functional status and increased comorbidity, which also show an independent association with increased toxicity. Published data may include several biases, such as referral and publication bias. Conclusions Decision making in elderly cancer patients should be based on the results of a geriatric assessment. Patients with few or no limitations should be treated as younger patients are treated. Data with a high level of evidence are unavailable for patients showing moderate or severe limitations in a geriatric assessment.
Collapse
Affiliation(s)
- Ulrich Wedding
- Klinik und Poliklinik fur Innere Medizin II, Department of Hematology and Oncology, Friedrich Schiller Universitat, Erlanger Allee 101, D-07747 Jena, Germany.
| | | | | | | | | |
Collapse
|
|
7
|
Geriatric factors analyses from FFCD 2001-02 phase III study of first-line chemotherapy for elderly metastatic colorectal cancer patients. Eur J Cancer 2017; 74:98-108. [DOI: 10.1016/j.ejca.2016.09.029] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Revised: 09/20/2016] [Accepted: 09/23/2016] [Indexed: 01/29/2023]
|
|
8
|
Moth EB, Vardy J, Blinman P. Decision-making in geriatric oncology: systemic treatment considerations for older adults with colon cancer. Expert Rev Gastroenterol Hepatol 2016; 10:1321-1340. [PMID: 27718755 DOI: 10.1080/17474124.2016.1244003] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Colon cancer is common and can be considered a disease of older adults with more than half of cases diagnosed in patients aged over 70 years. Decision-making about treatment with chemotherapy for older adults may be complicated by age-related physiological changes, impaired functional status, limited social supports, concerns regarding the occurrence of and ability to tolerate treatment toxicity, and the presence of comorbidities. This is compounded by a lack of high quality evidence guiding cancer treatment decisions for older adults. Areas covered: This narrative review evaluates the evidence for adjuvant and palliative systemic therapy in older adults with colon cancer. The value of an adequate assessment prior to making a treatment decision is addressed, with emphasis on the geriatric assessment. Guidance in making a treatment decision is provided. Expert commentary: Treatment decisions should consider goals of care, a patient's treatment preferences, and weigh up relative benefits and harms.
Collapse
Affiliation(s)
- Erin B Moth
- a Concord Cancer Centre , Concord Repatriation General Hospital , Sydney , Australia.,b Sydney Medical School , University of Sydney , Sydney , Australia
| | - Janette Vardy
- a Concord Cancer Centre , Concord Repatriation General Hospital , Sydney , Australia.,b Sydney Medical School , University of Sydney , Sydney , Australia
| | - Prunella Blinman
- a Concord Cancer Centre , Concord Repatriation General Hospital , Sydney , Australia.,b Sydney Medical School , University of Sydney , Sydney , Australia
| |
Collapse
|
|
9
|
Guion-Dusserre JF, Bertaut A, Ghiringhelli F, Vincent J, Quipourt V, Marilier S, Tharin Z, Bengrine-Lefevre L. Folfirinox in elderly patients with pancreatic or colorectal cancer-tolerance and efficacy. World J Gastroenterol 2016; 22:9378-9386. [PMID: 27895425 PMCID: PMC5107701 DOI: 10.3748/wjg.v22.i42.9378] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 08/14/2016] [Accepted: 09/28/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To study the tolerance and the efficiency of FOLFIRINOX in elderly patients diagnosed with colorectal or pancreatic cancer.
METHODS This retrospective study included elderly patients aged over 70 years of age treated at Georges-Francois Leclerc Center by FOLFIRINOX for histological proved colorectal or pancreatic cancer between January 2009 and January 2015. Chemotheapy regimen consisted of oxaliplatin (85 mg/m2 in over 120 min) followed by leucovorin (400 mg/m2 in over 120 min), with the addition, after 30 min of irinotecan (180 mg/m2 in over 90 min) then 5 fluorouracil (5FU) (400 mg/m2 administred intravenous bolus), followed by 5FU (2400 mg/m2 intraveinous infusion over 46 h) repeated every 2 wk. Geriatric parameters were recorded at the beginning. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events 4.03. Tumor response was evaluated by CT scan. Treatment continued until disease progression, unacceptable toxicities or patient refusal.
RESULTS Fifty-two patients aged from 70 to 87 years were treated by FOLFIRINOX, 34 had colorectal cancer and 18 had pancreatic cancer. Most of them were in good general condition, 82.7% had a 0-1 performance status and 61.5% had a Charlson Comorbidity Index < 10. The most frequent severe toxicities were neutropenia (17 patients, n = 32.7%) and diarrhea (35 patients n = 67.3%); 10 of the case of neutropenia and 5 of diarrhea registered a grade 4 toxicity. Thirty-nine patients (75%) initially received an adapted dose of chemotherapy. The dosage was adjusted for 26% of patients during the course of treatment. Tumor response evaluated by RECIST criteria showed a controlled disease for 25 patients (48.1%), a stable disease for 13 and a partial response for 12 patients. Time under treatment was higher for colorectal cancer with a median time of 2.44 mo (95%CI: 1.61-3.25). Overall survival was 43.88 mo for colorectal cancer and 12.51 mo for pancreatic cancer. In univariate or multivariate analysis, none of geriatric parameters were linked to overall survival. Only the type of tumor (pancreatic/colorectal) was linked in both analysis.
CONCLUSION For people over 70 years old, FOLFIRINOX regimen seems to induce manageable toxicities but similar, even higher, median survival rates compared to younger people.
Collapse
|
|
10
|
Obermannová R, Van Cutsem E, Yoshino T, Bodoky G, Prausová J, Garcia-Carbonero R, Ciuleanu T, Garcia Alfonso P, Portnoy D, Cohn A, Yamazaki K, Clingan P, Lonardi S, Kim TW, Yang L, Nasroulah F, Tabernero J. Subgroup analysis in RAISE: a randomized, double-blind phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab or placebo in patients with metastatic colorectal carcinoma progression. Ann Oncol 2016; 27:2082-2090. [PMID: 27573561 PMCID: PMC5091322 DOI: 10.1093/annonc/mdw402] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Revised: 07/27/2016] [Accepted: 08/10/2016] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The RAISE phase III clinical trial demonstrated that ramucirumab + FOLFIRI improved overall survival (OS) [hazard ratio (HR) = 0.844, P = 0.0219] and progression-free survival (PFS) (HR = 0.793, P < 0.0005) compared with placebo + FOLFIRI for second-line metastatic colorectal carcinoma (mCRC) patients previously treated with first-line bevacizumab, oxaliplatin, and a fluoropyrimidine. Since some patient or disease characteristics could be associated with differential efficacy or safety, prespecified subgroup analyses were undertaken. This report focuses on three of the most relevant ones: KRAS status (wild-type versus mutant), age (<65 versus ≥65 years), and time to progression (TTP) on first-line therapy (<6 versus ≥6 months). PATIENTS AND METHODS OS and PFS were evaluated by the Kaplan-Meier analysis, with HR determined by the Cox proportional hazards model. Treatment-by-subgroup interaction was tested to determine whether treatment effect was consistent between subgroup pairs. RESULTS Patients with both wild-type and mutant KRAS benefited from ramucirumab + FOLFIRI treatment over placebo + FOLFIRI (interaction P = 0.526); although numerically, wild-type KRAS patients benefited more (wild-type KRAS: median OS = 14.4 versus 11.9 months, HR = 0.82, P = 0.049; mutant KRAS: median OS = 12.7 versus 11.3 months, HR = 0.89, P = 0.263). Patients with both longer and shorter first-line TTP benefited from ramucirumab (interaction P = 0.9434), although TTP <6 months was associated with poorer OS (TTP ≥6 months: median OS = 14.3 versus 12.5 months, HR = 0.86, P = 0.061; TTP <6 months: median OS = 10.4 versus 8.0 months, HR = 0.86, P = 0.276). The subgroups of patients ≥65 versus <65 years also derived a similar ramucirumab survival benefit (interaction P = 0.9521) (≥65 years: median OS = 13.8 versus 11.7 months, HR = 0.85, P = 0.156; <65 years: median OS = 13.1 versus 11.9 months, HR = 0.86, P = 0.098). The safety profile of ramucirumab + FOLFIRI was similar across subgroups. CONCLUSIONS These analyses revealed similar efficacy and safety among patient subgroups with differing KRAS mutation status, longer or shorter first-line TTP, and age. Ramucirumab is a beneficial addition to second-line FOLFIRI treatment for a wide range of patients with mCRC. TRIAL REGISTRATION ClinicalTrials.gov, NCT01183780.
Collapse
Affiliation(s)
- R Obermannová
- Masaryk Memorial Cancer Institute, Brno, Czech Republic
| | - E Van Cutsem
- University Hospitals Leuven and KU Leuven, Leuven, Belgium
| | - T Yoshino
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
| | - G Bodoky
- Department of Oncology, St László Hospital, Budapest, Hungary
| | - J Prausová
- Onocology Clinic, Charles University, Prague, Czech Republic
| | - R Garcia-Carbonero
- Department of Oncology, Hospital Universitario Doce de Octubre, Madrid, Spain
| | - T Ciuleanu
- Institutul Oncologic Ion Chiricuta and UMF, Cluj-Napoca, Romania
| | - P Garcia Alfonso
- Department of Oncology, Hospital General Universitario Gregorio Maraňón, Madrid, Spain
| | - D Portnoy
- The West Clinic-University of Tennessee Health Sciences Center, Memphis
| | - A Cohn
- Rocky Mountain Cancer Center, Denver, USA
| | - K Yamazaki
- Department of Gastrointestinal Oncology, Shizouka Cancer Center, Shizouka, Japan
| | - P Clingan
- Southern Medical Day Care Centre, Wollongong, NSW, Australia
| | - S Lonardi
- Department of Medical Oncology, Istituto Oncologico Veneto-IRCCS, Padova, Italy
| | - T W Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - L Yang
- Eli Lilly and Company, Bridgewater, USA
| | - F Nasroulah
- Eli Lilly and Company, Buenos Aires, Argentine Republic
| | - J Tabernero
- Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain
| |
Collapse
|
|
11
|
Aparicio T, Lavau-Denes S, Phelip JM, Maillard E, Jouve JL, Gargot D, Gasmi M, Locher C, Adhoute X, Michel P, Khemissa F, Lecomte T, Provençal J, Breysacher G, Legoux JL, Lepère C, Charneau J, Cretin J, Chone L, Azzedine A, Bouché O, Sobhani I, Bedenne L, Mitry E. Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001-02). Ann Oncol 2016; 27:121-127. [PMID: 26487578 DOI: 10.1093/annonc/mdv491] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Accepted: 10/08/2015] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients. PATIENTS AND METHODS Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR). RESULTS From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%). CONCLUSION In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2. CLINICALTRIALSGOV NCT00303771.
Collapse
Affiliation(s)
- T Aparicio
- Department of Gastroenterology, CHU Avicenne, APHP and University Paris 13, Sorbonne Paris Cité, Bobigny
| | | | - J M Phelip
- Department of Gastroenterology, CHU Saint Etienne-Hôpital Nord, Saint Priest en Jarez
| | - E Maillard
- FFCD Data Center, Fédération Francophone de Cancérologie Digestive, Dijon
| | - J L Jouve
- Department of Gastroenterology, CHU Le Bocage, Dijon
| | - D Gargot
- Department of Gastroenterology, CH Blois, Blois
| | - M Gasmi
- Department of Gastroenterology, CHU Hôpital Nord, Marseille
| | - C Locher
- Department of Gastroenterology, CH Meaux, Meaux
| | - X Adhoute
- Department of Gastroenterology, CHU Haut Lévèque, Pessac
| | - P Michel
- Department of Gastroenterology, CHU Charles Nicolle, Rouen
| | - F Khemissa
- Department of Gastroenterology, CH Saint Jean, Perpignan
| | - T Lecomte
- Department of Gastroenterology, CHU Trousseau, Tours
| | - J Provençal
- Department of Oncology, CH Chambery, Chambery
| | - G Breysacher
- Department of Gastroenterology, CH Pasteur, Colmar
| | - J L Legoux
- Department of Gastroenterology, CH de la Source, Orléans
| | - C Lepère
- Department of Digestive Oncology, CHU Georges Pompidou, APHP, Paris
| | - J Charneau
- Department of Gastroenterology, CH Duchenne, Boulogne sur Mer
| | - J Cretin
- Department of Oncology, Clinique Bonnefon, Alès
| | - L Chone
- Department of Gastroenterology, CHU Nancy, Vandoeuvre-les-Nancy
| | - A Azzedine
- Department of Gastroenterology, CH Avignon, Avignon
| | - O Bouché
- Department of Gastroenterology, CHU Robert Debré, Reims
| | - I Sobhani
- Department of Gastroenterology, CHU Henri Mondor, APHP, Créteil
| | - L Bedenne
- FFCD Data Center, Fédération Francophone de Cancérologie Digestive, Dijon Department of Gastroenterology, CHU Le Bocage, Dijon
| | - E Mitry
- Department of Oncology, Institut Curie, Saint-Cloud University Versailles-St Quentin, St Quentin, France
| |
Collapse
|
|
12
|
Bossé D, Vickers M, Lemay F, Beaudoin A. Palliative chemotherapy for patients 70 years of age and older with metastatic colorectal cancer: a single-centre experience. ACTA ACUST UNITED AC 2015; 22:e349-56. [PMID: 26628875 DOI: 10.3747/co.22.2337] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Metastatic colorectal cancer (mcrc) commonly affects elderly people, an understudied subset of patients. We analyzed the survival impact of the first and subsequent lines of chemotherapy in eligible non-trial patients 70 years of age and older with mcrc treated between 2004 and 2012. METHODS This single-centre retrospective analysis estimated overall survival (os) and progression-free survival (pfs) using the Kaplan-Meier method. Multivariate analysis was used to adjust for age, sex, Eastern Cooperative Oncology Group performance status, score on the Charlson comorbidity index, dependency in activities of daily living, and exposure to 1 or more chemotherapy doublets, capecitabine alone, or best supportive care (bsc). RESULTS Of 109 patients identified, 29 elected bsc, and 80 received chemotherapy. In multivariate analysis, age was not associated with os [hazard ratio (hr): 0.99; 95% confidence interval (ci): 0.92 to 1.05], but a performance status of 2 or higher was associated with a decreased likelihood of survival (hr: 3.12; 95% ci: 1.87 to 5.76), and exposure to 1 or more doublets was associated with improved survival (hr: 0.33; 95% ci: 0.17 to 0.66). In univariate analysis, a trend toward improved os was observed for first-line doublet chemotherapy compared with capecitabine (hr: 0.66; 95% ci: 0.41 to 1.07), and pfs was superior (hr: 0.46; 95% ci: 0.26 to 0.84). Compared with exposure to 1 doublet, exposure to the 3 potential cytotoxic chemotherapies was not associated with improved os (hr: 0.77; 95% ci: 0.41 to 1.43). The incidence of neutropenia with first-line folfiri was 40%; the incidences of bevacizumab-related arterial and venous thrombosis were both 8%. CONCLUSIONS Exposure to 1 or more doublet chemotherapies for mcrc was associated with better outcomes in non-trial patients 70 years of age and older. Elderly patients treated with palliative chemotherapy and bevacizumab should be monitored carefully for arterial and venous thrombotic events.
Collapse
Affiliation(s)
- D Bossé
- Department of Medicine, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC
| | - M Vickers
- Ottawa Regional Cancer Centre, Ottawa, ON
| | - F Lemay
- Gastroenterology Division, Department of Medicine, Centre hospitalier universitaire de Sherbrooke and Centre de recherche clinique Étienne-Le Bel, Sherbrooke, QC
| | - A Beaudoin
- Gastroenterology Division, Department of Medicine, Centre hospitalier universitaire de Sherbrooke and Centre de recherche clinique Étienne-Le Bel, Sherbrooke, QC
| |
Collapse
|
|
13
|
Rosati G, Aprile G, Poletto E, Avallone A. An update on the management of metastatic colorectal cancer in the elderly. COLORECTAL CANCER 2014. [DOI: 10.2217/crc.14.32] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
SUMMARY The availability of new chemotherapeutic and targeted agents has changed the life expectancy of patients with metastatic colorectal cancer thanks to the possibility of sequentially administering fluoropyrimidines combined with irinotecan and oxaliplatin plus monoclonal antibodies. This approach is seldom feasible in the elderly, especially because of the poor tolerability of some agents. Frail patients should only receive palliative treatment. Oppositely, fit elderly patients can be treated with more aggressive therapies, similarly to the younger ones. What is not sufficiently known is how to manage the elderly categorized as intermediate. In the coming years, it appears necessary how to accurately differentiate the elderly through a comprehensive geriatric assessment performed with validated scales and uniformed criteria simpler than those currently available.
Collapse
Affiliation(s)
- Gerardo Rosati
- Medical Oncology Unit, S. Carlo Hospital, Potenza, Italy
| | - Giuseppe Aprile
- Department of Medical Oncology, University Hospital, Udine, Italy
| | - Elena Poletto
- Department of Medical Oncology, University Hospital, Udine, Italy
| | - Antonio Avallone
- Department of Gastrointestinal Medical Oncology, National Cancer Institute, Naples, Italy
| |
Collapse
|
|
14
|
Colon Cancer in Older Adults: A Primer for Geriatricians. CURRENT GERIATRICS REPORTS 2014. [DOI: 10.1007/s13670-014-0087-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
|
|
15
|
McCleary NJ, Dotan E, Browner I. Refining the Chemotherapy Approach for Older Patients With Colon Cancer. J Clin Oncol 2014; 32:2570-80. [DOI: 10.1200/jco.2014.55.1960] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Population studies support an increased incidence of most cancers among older adults. Colorectal cancer has high prevalence in the aging population, with a median age of 69 years at diagnosis and 74 years at death. The vast majority of patients with colon cancer (CC) will require chemotherapy treatments during their disease course, challenging oncologists with the task of tailoring therapy for older patients with CC in the face of limited evidence-based data to guide them. Factors such as comorbidity, performance status, cognitive function, and social support may affect decision making and complicate tolerance of any recommended therapy. In recent years, attention to the specific needs of the aging population with cancer has given rise to the field of geriatric oncology in general, and has generated an increasing fund of knowledge on which to base chemotherapy delivery for this specific population of patients with CC. This article will review the available data specifically for chemotherapy management of older patients with CC in the postoperative and metastatic settings.
Collapse
Affiliation(s)
- Nadine J. McCleary
- Nadine J. McCleary, Dana-Farber Cancer Institute, Boston MA; Efrat Dotan, Fox Chase Cancer Center, Philadelphia, PA; and Ilene Browner, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD
| | - Efrat Dotan
- Nadine J. McCleary, Dana-Farber Cancer Institute, Boston MA; Efrat Dotan, Fox Chase Cancer Center, Philadelphia, PA; and Ilene Browner, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD
| | - Ilene Browner
- Nadine J. McCleary, Dana-Farber Cancer Institute, Boston MA; Efrat Dotan, Fox Chase Cancer Center, Philadelphia, PA; and Ilene Browner, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD
| |
Collapse
|
|
16
|
First-line bevacizumab and capecitabine-oxaliplatin in elderly patients with mCRC: GEMCAD phase II BECOX study. Br J Cancer 2014; 111:241-8. [PMID: 24946000 PMCID: PMC4102952 DOI: 10.1038/bjc.2014.346] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2014] [Revised: 05/12/2014] [Accepted: 05/27/2014] [Indexed: 12/13/2022] Open
Abstract
Background: Subgroup analyses of clinical studies suggest that bevacizumab plus XELOX is effective and tolerable in elderly patients with metastatic colorectal cancer (mCRC). The prospective BECOX study examined the efficacy and safety of bevacizumab plus XELOX, followed by bevacizumab plus capecitabine in elderly patients with mCRC. Methods: Patients aged ⩾70 years with Eastern Cooperative Oncology Group performance status 0 out of 1 and confirmed mCRC were included. Patients received bevacizumab 7.5 mg kg−1 and oxaliplatin 130 mg m−2 on day 1, plus capecitabine 1000 mg m−2 bid orally on days 1–14 every 21 days; oxaliplatin was discontinued after 6 cycles. The primary end point was time to progression (TTP). Results: The intent-to-treat population comprised 68 patients (65% male, median age 76 years). Median TTP was 11.1 months; median overall survival was 20.4 months; overall response rate was 46%. Grade 3 or 4 adverse events included diarrhoea (18%) and asthenia (16%). Grade 3 or 4 adverse events of special interest for bevacizumab included deep-vein thrombosis (6%) and pulmonary embolism (4%). Conclusions: Bevacizumab plus XELOX was effective and well tolerated in elderly patients in the BECOX study. The adverse-event profile was similar to previous reports; no new safety concerns were identified. Fit elderly patients with mCRC should be considered for treatment with bevacizumab plus XELOX.
Collapse
|
|
17
|
Varol U, Dirican A, Yildiz I, Oktay E, Degirmenci M, Alacacioglu A, Barutca S, Karabulut B, Uslu R. First-line mono-chemotherapy in frail elderly patients with metastatic colorectal cancer. Asian Pac J Cancer Prev 2014; 15:3157-61. [PMID: 24815463 DOI: 10.7314/apjcp.2014.15.7.3157] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Unlike for fit elderly metastatic colorectal cancer (mCRC) patients, general approaches to initial treatment for the frail older mCRC patients are not clear. Our aim was to evaluate the efficiency and safety of first-line single-agent treatment in one such group. MATERIALS AND METHODS We retrospectively evaluated mCRC patients aged 70 or older with an Eastern Cooperative Oncology Group performance score of 2. They had no prior treatment and underwent first-line single-agent capecitabine or other monotherapies until disease progression or unacceptable toxicity. RESULTS Thirty-six patients were included. Most (n:28, 77.8%) were treated with capecitabine. One patient achieved a complete response and 5 patients had a partial response for an overall response rate of 16.6%. Twelve patients (33.3%) remained stable. Median progression free survival was 5 months (confidence interval (CI), %; 3.59-6.40) and median overall survival was 10 months (95 CI%; 8.1-11.8). Grade 3-4 toxicity was found in 6 patients (16.6%). Febrile neutropenia was not observed and there were no toxicity-associated deaths. CONCLUSIONS Capecitabine is a safe chemotherapeutic agent with moderate activity for first-line treatment of older metastatic colorectal cancer patients with limited performance status.
Collapse
Affiliation(s)
- Umut Varol
- Katip Celebi University Ataturk, Izmir, Turkey E-mail :
| | | | | | | | | | | | | | | | | |
Collapse
|
|
18
|
Moriya H, Saito K, Helsby N, Sugino S, Yamakage M, Sawaguchi T, Takasaki M, Kato H, Kurosawa N. Association between the low-dose irinotecan regimen-induced occurrence of grade 4 neutropenia and genetic variants of UGT1A1 in patients with gynecological cancers. Oncol Lett 2014; 7:2035-2040. [PMID: 24932285 PMCID: PMC4049750 DOI: 10.3892/ol.2014.2046] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2013] [Accepted: 02/20/2014] [Indexed: 12/14/2022] Open
Abstract
The occurrence of severe neutropenia during treatment with irinotecan (CPT-11) is associated with the *6 and *28 alleles of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). However, the correlation between these variants and the occurrence of severe neutropenia in a low-dose CPT-11 regimen for the treatment of gynecological cancers has not been extensively studied. There are also no studies regarding the association between the 421C>A mutation in ATP-binding cassette sub-family G member 2 (ABCG2) and the occurrence of severe neutropenia in CPT-11-treated patients with gynecological cancers. The present study was designed to determine the factors associated with the occurrence of grade 4 neutropenia during chemotherapy for gynecological cancers with combinations of CPT-11 and cisplatin or mitomycin C. In total, 44 patients with gynecological cancer were enrolled in the study. The association between the absolute neutrophil count (ANC) nadir values, the total dose of CPT-11 and the genotypes of UGT1A1 or ABCG2 was studied. No correlation was observed between the ANC nadir values and the total dose of CPT-11. The ANC nadir values in the UGT1A1*6/*28 and *6/*6 groups were significantly lower compared with those in the *1/*1 group (P<0.01). Univariate analysis showed no association between the occurrence of grade 4 neutropenia and the ABCG2 421C>A mutation. Subsequent to narrowing the factors by univariate analysis, multivariate logistic regression analysis only detected significant correlations between the occurrence of grade 4 neutropenia and the UGT1A1*6/*6 and *6/*28 groups (P=0.029; odds ratio, 6.90; 95% confidence interval, 1.22-38.99). No associations were detected between the occurrence of grade 4 neutropenia and the heterozygous variant (*1/*6 or *1/*28) genotype, type of regimen or age. In conclusion, the UGT1A1*6/*28 and *6/*6 genotypes were found to be associated with the occurrence of severe neutropenia in the low-dose CPT-11 regimen for gynecological cancers. This finding indicates that the determination of UGT1A1 variants may be as useful in CPT-11 chemotherapy for gynecological conditions as it is in colorectal and lung cancer patients treated with this drug.
Collapse
Affiliation(s)
- Hiroyuki Moriya
- Department of Pharmacy, Hokkaido Pharmaceutical University School of Pharmacy, Otaru, Japan
| | - Katsuhiko Saito
- Department of Pharmacy, Hokkaido Pharmaceutical University School of Pharmacy, Otaru, Japan
| | - Nuala Helsby
- Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Shigekazu Sugino
- Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Michiaki Yamakage
- Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Takeru Sawaguchi
- Department of Pharmacy, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan
| | - Masahiko Takasaki
- Department of Pharmacy, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan
| | - Hidenori Kato
- Department of Gynecology, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan
| | - Nahoko Kurosawa
- Department of Pharmacy, Hokkaido Pharmaceutical University School of Pharmacy, Otaru, Japan
| |
Collapse
|
|
19
|
Benavides M, Berciano-Guerrero M. Elderly patients with metastatic colorectal cancer: overall issues and first-line chemotherapy options. COLORECTAL CANCER 2013. [DOI: 10.2217/crc.13.69] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
SUMMARY The aging phenomenon is resulting in an ever greater incidence of colorectal cancer (CRC) in the elderly. Chronologic age is not the best or only way to define elderly patients because aging varies greatly. Comprehensive geriatric assessment has proved beneficial for more appropriate therapeutic options although its influence on treatment decisions and outcomes remains to be validated. Fit elderly patients with metastatic CRC derive similar benefits to their younger counterparts, but only one Phase III trial exists to define the best treatment. New strategies such as maintenance therapies, which are particularly appropriate in these patients, are needed. As very few data are available for the vulnerable/frail elderly population, it is important to better define these terms and the efficacy (if any) of treatment modalities in this group. Translational research in geriatric oncology must be improved in this heterogeneous population to identify biological and clinical correlates of cancer and aging, ameliorating personalized treatment in elderly metastatic CRC patients.
Collapse
Affiliation(s)
- Manuel Benavides
- Medical Oncology Department, Hospital Regional Universitario Carlos Haya, Málaga, Spain
| | | |
Collapse
|
|
20
|
Benavides M, Pericay C, Valladares-Ayerbes M, Gil-Calle S, Massutí B, Aparicio J, Dueñas R, González-Flores E, Carrato A, Marcuello E, Gómez A, Cabrera E, Queralt B, Gómez MJ, Guasch I, Etxeberría A, Alfaro J, Campos JM, Reina JJ, Aranda E. Oxaliplatin in Combination With Infusional 5-Fluorouracil as First-Line Chemotherapy for Elderly Patients With Metastatic Colorectal Cancer: A Phase II Study of the Spanish Cooperative Group for the Treatment of Digestive Tumors. Clin Colorectal Cancer 2012; 11:200-6. [DOI: 10.1016/j.clcc.2012.01.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2011] [Revised: 12/22/2011] [Accepted: 01/20/2012] [Indexed: 01/06/2023]
|
|
21
|
Sastre J, Grávalos C, Rivera F, Massuti B, Valladares-Ayerbes M, Marcuello E, Manzano JL, Benavides M, Hidalgo M, Díaz-Rubio E, Aranda E. First-line cetuximab plus capecitabine in elderly patients with advanced colorectal cancer: clinical outcome and subgroup analysis according to KRAS status from a Spanish TTD Group Study. Oncologist 2012; 17:339-45. [PMID: 22363067 DOI: 10.1634/theoncologist.2011-0406] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
UNLABELLED Single-agent cetuximab is safe and active in elderly patients with advanced colorectal cancer (CRC). A cetuximab-capecitabine combination has not previously been tested in elderly patients with advanced CRC. MATERIAL AND METHODS Sixty-six patients with advanced CRC were treated with cetuximab as a 400 mg/m2 i.v. infusion followed by 250 mg/m2 i.v. weekly plus capecitabine at a dose of 1,250 mg/m2 every 12 hours. After the inclusion of 27 patients, the protocol was amended for safety reasons, reducing the dose of capecitabine to 1,000 mg/m2 every 12 hours. Thirty-nine additional patients were treated with the reduced dose of capecitabine. RESULTS The overall response rate was 31.8%. KRAS status was determined in 58 patients (88%). Fourteen of 29 patients with wild-type KRAS tumors responded (48.3%; 95% confidence interval [CI], 29.4%-67.5%), compared with six of 29 patients with mutant KRAS tumors (20.7%; 95% CI, 8.0%-39.7%). The median progression-free survival (PFS) interval was 7.1 months. The median PFS interval for patients whose tumors were wild-type KRAS was significantly longer than for those with mutant KRAS tumors (8.4 months versus 6.0 months; p = .024). The high incidence of severe paronychia (29.6%) declined (7.7%) after capecitabine dose adjustment. CONCLUSIONS Cetuximab plus capecitabine at a dose of 1,000 mg/m2 every 12 hours may be an alternative to more aggressive regimens in elderly patients with advanced wild-type KRAS CRC.
Collapse
Affiliation(s)
- Javier Sastre
- Medical Oncology Department, Hospital Clínico San Carlos, Calle Martín Lagos s/n 28040 Madrid, Spain.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
22
|
Tam VC, Rask S, Koru-Sengul T, Dhesy-Thind S. Generalizability of toxicity data from oncology clinical trials to clinical practice: toxicity of irinotecan-based regimens in patients with metastatic colorectal cancer. ACTA ACUST UNITED AC 2011; 16:13-20. [PMID: 20016742 PMCID: PMC2794679 DOI: 10.3747/co.v16i6.426] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Background The relevance of oncology trial results to clinical practice depends on whether the trial participants are similar to the actual population of patients receiving treatment for the malignancy and whether the patients are treated similarly in both circumstances. Chemotherapy treatments may be more toxic in patients of advanced age and poor performance status—patients typically excluded from clinical trials. Methods In a retrospective chart review that included all non-trial patients with metastatic colorectal cancer treated with irinotecan-based chemotherapy from January 2004 to September 2006 at our institution, we quantified and subsequently compared the toxicity rates of the irinotecan regimens in clinical practice with published toxicity rates from corresponding phase iii clinical trials. The primary endpoint was the incidence of grades 3 and 4 diarrhea. Results The study included 203 patients, and the irinotecan regimens considered included
folfiri [irinotecan, leucovorin, 5-fluorouracil (5fu)], ifl (bevacizumab, irinotecan, 5fu, leucovorin), xeliri (capecitabine, 3-weekly irinotecan), and irinotecan monotherapy. The rates of grades 3 and 4 diarrhea for folfiri, ifl, xeliri, and irinotecan monotherapy in clinical practice were 10%, 15%, 17%, and 21% as compared with 10%, 23%, 20%, and 31% respectively in clinical trials. When only patients meeting trial performance status and age criteria were analyzed, the rates of grades 3 and 4 diarrhea by regimen were 11%, 20%, 19%, and 26% respectively. Conclusions Overall, the toxicity rates for folfiri and irinotecan monotherapy in non-trial patients were not statistically different from the rates quoted in published clinical trials.
Collapse
Affiliation(s)
- V C Tam
- Department of Medicine, McMaster University, Hamilton, ON
| | | | | | | |
Collapse
|
|
23
|
Rousseau F, Bugat R, Ducreux M, Cvitkovic F, Carola E, Gisselbrecht M, Viret F, Esterni B, Genève J, Brain E. Effect of XELOX on functional ability among elderly patients with metastatic colorectal cancer: Results from the FNCLCC/GERICO 02 phase II study. J Geriatr Oncol 2011. [DOI: 10.1016/j.jgo.2010.11.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
|
|
24
|
Kuboki Y, Mizunuma N, Ozaka M, Ogura M, Suenaga M, Shinozaki E, Matsusaka S, Chin K, Matsuura M, Hatake K. Grade 3/4 neutropenia is a limiting factor in second-line FOLFIRI following FOLFOX4 failure in elderly patients with metastatic colorectal cancer. Oncol Lett 2011; 2:493-498. [PMID: 22866109 DOI: 10.3892/ol.2011.260] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2010] [Accepted: 02/02/2011] [Indexed: 01/31/2023] Open
Abstract
Previous studies have reported improved outcomes for elderly patients with metastatic colorectal cancer (mCRC) treated with oxaliplatin or irinotecan as first-line chemotherapy. However, few studies regarding second-line chemotherapy with oxaliplatin or irinotecan are currenlty available. We analyzed retrospectively the efficacy and toxicity in elderly patients (median age, 74 years) treated with second-line FOLFIRI following first-line FOLFOX4 failure. From March 2005 to January 2008, 35 elderly patients with mCRC received first-line FOLFOX4 comprising leucovorin, 5-FU and oxaliplatin followed by second-line FOLFIRI comprising leucovorin, 5-FU and irinotecan. The median number of treatment courses with FOLFIRI was 5 (range 2-32). One patient responded to the treatment. The disease control rate was 38.2%. The median time to treatment failure was 3 months, and the median overall survival (OS) time from the beginning of first-line chemotherapy was 20.7 months. The incidence of grade 3/4 neutropenia was 71.4%, while febrile neutropenia was 11.4%. The incidence of non-hematological toxicity was low. The use of the three active drugs, 5-FU, oxaliplatin and irinotecan, in mCRC produced the longest OS in elderly as well as in younger patients. However, the elderly patients treated with second-line FOLFIRI had a high rate of hematological toxicity. Second-line FOLFIRI may therefore be used with caution in the elderly.
Collapse
Affiliation(s)
- Yasutoshi Kuboki
- Department of Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
25
|
Vamvakas L, Athanasiadis A, Karampeazis A, Kakolyris S, Polyzos A, Kouroussis C, Ziras N, Kalbakis K, Georgoulias V, Souglakos J. Clinical outcome of elderly patients with metastatic colorectal cancer treated with FOLFOXIRI versus FOLFIRI: Subgroup analysis of a randomized phase III trial from the Hellenic Oncology Research Group (HORG). Crit Rev Oncol Hematol 2010; 76:61-70. [DOI: 10.1016/j.critrevonc.2009.08.003] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2009] [Revised: 05/21/2009] [Accepted: 08/11/2009] [Indexed: 01/08/2023] Open
|
|
26
|
Mohile SG, Kaur HP, Goldberg RM. Management of colon and rectal cancer in older adults. PRACTICAL GERIATRIC ONCOLOGY 2010:148-170. [DOI: 10.1017/cbo9780511763182.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
27
|
Nguyen HL, Hwang J. Treatment of metastatic colorectal cancer in the elderly. Curr Treat Options Oncol 2010; 10:287-95. [PMID: 19821033 DOI: 10.1007/s11864-009-0111-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
OPINION STATEMENT Metastatic colorectal cancer (CRC) is the second leading cause of cancer related mortality in the United States. The median age of patients at diagnosis is over 70, so as the American population ages, it can be expected that the incidence of CRC will also increase. There is limited prospective data regarding the safety and efficacy of chemotherapy in elderly patients with metastatic CRC. However, the data that are available suggest that elderly patients with a good performance status have a similar likelihood of response to currently available chemotherapy, though perhaps a somewhat higher likelihood of toxicities such as myelosuppression. This paper reviews the available data and recommendations for the treatment of this patient population.
Collapse
Affiliation(s)
- Hong L Nguyen
- Division of Hematology/Oncology, Lombardi Comprehensive Cancer Center, 3800 Reservoir Road, NW, Washington, DC 20007, USA
| | | |
Collapse
|
|
28
|
De Santis M, Bellmunt J, Mead G, Kerst JM, Leahy M, Maroto P, Skoneczna I, Marreaud S, de Wit R, Sylvester R. Randomized phase II/III trial assessing gemcitabine/ carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer "unfit" for cisplatin-based chemotherapy: phase II--results of EORTC study 30986. J Clin Oncol 2009; 27:5634-9. [PMID: 19786668 DOI: 10.1200/jco.2008.21.4924] [Citation(s) in RCA: 134] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
PURPOSE There is no standard treatment for patients with advanced urothelial cancer who are ineligible ("unfit") for cisplatin-based chemotherapy (CHT). To compare the activity and safety of two CHT combinations in this patient group, a randomized phase II/III trial was conducted by the EORTC (European Organisation for Research and Treatment of Cancer). We report here the phase II results of the study. PATIENTS AND METHODS CHT-naïve patients with measurable disease and impaired renal function (30 mL/min < glomerular filtration rate [GFR] < 60 mL/min) and/or performance status (PS) 2 were randomly assigned to receive either GC (gemcitabine 1,000 mg/m(2) on days 1 and 8 and carboplatin area under the serum concentration-time curve [AUC] 4.5) for 21 days or M-CAVI (methotrexate 30 mg/m(2) on days 1, 15, and 22; carboplatin AUC 4.5 on day 1; and vinblastine 3 mg/m(2) on days 1, 15, and 22) for 28 days. End points of response and severe acute toxicity (SAT) were evaluated with respect to treatment group, renal function, PS, and Bajorin risk groups. RESULTS Three of 178 patients who were ineligible or did not start treatment were excluded. SAT was reported in 13.6% of patients on GC and in 23% on M-CAVI. Overall response rates were 42% (37 of 88) for GC and 30% (26 of 87) for M-CAVI. Patients with PS 2 and GFR less than 60 mL/min and patients in Bajorin risk group 2 showed a response rate of only 26% and 20% and an SAT rate of 26% and 25%, respectively. CONCLUSION Both combinations are active in this group of unfit patients. However, patients with PS 2 and GFR less than 60 mL/min do not benefit from combination CHT. Alternative treatment modalities should be sought in this subgroup of poor-risk patients.
Collapse
Affiliation(s)
- Maria De Santis
- Kaiser Franz Josef Hospital and Applied Cancer Research-Institution for Translational Research, Ludwig Boltzmann-Institute for Applied Cancer Research, Vienna, Austria.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
29
|
Rosati G, Cordio S, Bordonaro R, Caputo G, Novello G, Reggiardo G, Manzione L. Capecitabine in combination with oxaliplatin or irinotecan in elderly patients with advanced colorectal cancer: results of a randomized phase II study. Ann Oncol 2009; 21:781-786. [PMID: 19713248 DOI: 10.1093/annonc/mdp359] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND To determine the efficacy and tolerability of capecitabine combined with oxaliplatin (CAPOX) or irinotecan (CAPIRI) as first-line treatment in patients with advanced/metastatic colorectal cancer aged > or =70 years. PATIENTS AND METHODS Patients aged > or =70 years were randomly assigned to receive CAPOX [oxaliplatin 65 mg/m(2) intravenously (i.v.) days 1 and 8 and capecitabine 1000 mg/m(2) orally b.i.d. days 1-14; q21d] or CAPIRI (irinotecan 80 mg/m(2) i.v. days 1 and 8 and capecitabine 1000 mg/m(2) orally b.i.d. days 1-14; q21d). The primary study end point was overall response rate (ORR). RESULTS Ninety-four patients were enrolled. In an intent-to-treat analysis, 2 complete responses (CRs) and 16 partial responses (PRs) were reported with CAPOX (ORR 38%), and 2 CRs and 15 PRs with CAPIRI (ORR 36%; P = 0.831). Median time to progression was 8 months for CAPOX and 7 months for CAPIRI (P = 0.195), with median survival times of 19.3 months and 14.0 months (P = 0.165), respectively. Global health status was improved in 45% and in 21% of patients in the CAPOX and CAPIRI arms, respectively. The most common treatment-related grade 3-4 adverse events in CAPIRI versus CAPOX patients were diarrhea (32% versus 15%; P = 0.052) and neutropenia (23% versus 6%; P = 0.021). CONCLUSION CAPOX and CAPIRI had similar efficacy in elderly patients, although CAPOX seemed to be better tolerated.
Collapse
Affiliation(s)
- G Rosati
- Medical Oncology Unit, S. Carlo Hospital, Potenza.
| | - S Cordio
- Medical Oncology Unit, Garibaldi Nesima Hospital
| | - R Bordonaro
- Medical Oncology Unit, Vittorio Emanuele Hospital, Catania
| | - G Caputo
- Medical Oncology Unit, Garibaldi Nesima Hospital
| | - G Novello
- Medical Oncology Unit, Vittorio Emanuele Hospital, Catania
| | - G Reggiardo
- Biostatistic Unit Medi Service, Genova, Italy
| | - L Manzione
- Medical Oncology Unit, S. Carlo Hospital, Potenza
| |
Collapse
|
|
30
|
Jackson NA, Barrueco J, Soufi-Mahjoubi R, Marshall J, Mitchell E, Zhang X, Meyerhardt J. Comparing safety and efficacy of first-line irinotecan/fluoropyrimidine combinations in elderly versus nonelderly patients with metastatic colorectal cancer. Cancer 2009; 115:2617-29. [DOI: 10.1002/cncr.24305] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
|
|
31
|
Abstract
Elderly patients will be the largest group of oncology patients in the future. Because of minimal participation of older patients in randomized clinical trials there is a lack of evidence-based data to make correct decisions with regard to chemotherapy and/or targeted therapy in this age group. Elderly patients have similar benefits from systemic therapies as younger counterparts, but many elders have substantial co-morbidities, which may limit the life expectancy and the effectiveness of systemic therapy. Close collaboration between oncologists and geriatrists will help make decisions on the management of elderly patients suffering from cancer.
Collapse
Affiliation(s)
- László Landherr
- Fovárosi Onkormányzat Uzsoki utcai Kórháza Onkoradiológiai Központ 1145 Budapest Uzsoki u. 29-41.
| | | |
Collapse
|
|
32
|
Aschele C, Bergamo F, Lonardi S. Chemotherapy for operable and advanced colorectal cancer. Cancer Treat Rev 2009; 35:509-16. [PMID: 19481872 DOI: 10.1016/j.ctrv.2009.04.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
The majority of colorectal cancer patients receive chemotherapy either to palliate advanced unresectable disease or to reduce the risk of recurrence after radical surgery. Thanks to the improvements in systemic chemotherapy, in the last 20 years the median survival time for patients with unresectable metastatic disease has indeed progressively increased from less than 6 to almost 24 months and recurrences after radical surgery in patients with early-stage tumors have been halved. Although colorectal cancer incidence increase with aging, there is limited scientific evidence based on prospective clinical trials to guide the management of elderly colorectal cancer patients. In addition, aging is a continuum process making strict cut-off difficult to define and homogeneous subgroups hard to identify. There is significant heterogeneity also as regards comorbidities, overall physical ability, mental health and functional status. Specific guidelines for the medical treatment of elderly colorectal cancer patients are therefore difficult to draw. While fit patients are generally treated with adult protocols and frail individuals rarely receive chemotherapy, managing the intermediate vulnerable patients requires a careful balance between the biological and psycho-social costs of treatment, the aggressiveness of the tumor and its perception by the patient. In this review, the major achievements of chemotherapy in the treatment of colorectal cancer will be described and the available data addressing the extension of these chemotherapy programs to elderly patients will be discussed. Special emphasis will be given to the development of specific treatment strategies depending on the degree of disease aggressiveness. Empirical suggestions to adapt the chemotherapy programs developed for adult fit patients to subjects with various degrees of vulnerability and frailty will also be given along with practical indications for the use of specific chemotherapeutic agents in the presence of some common elderly-related comorbidities.
Collapse
Affiliation(s)
- Carlo Aschele
- Medical Oncology Unit, E.O. Ospedali Galliera, 16128 Genova, Italy.
| | | | | |
Collapse
|
|
33
|
Saif MW, Lichtman SM. Chemotherapy options and outcomes in older adult patients with colorectal cancer. Crit Rev Oncol Hematol 2009; 72:155-69. [PMID: 19356946 DOI: 10.1016/j.critrevonc.2009.02.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2008] [Revised: 02/05/2009] [Accepted: 02/19/2009] [Indexed: 11/19/2022] Open
Abstract
The majority of patients with colorectal cancer (CRC) are >/=65 years of age, yet older patients with CRC remain under-represented in clinical trials. Older adult patients may be more likely than younger patients to experience chemotherapy-related toxicities due to factors such as existing comorbidities, incompatibility of chemotherapy with other medications, and age-related reduction in the detoxification and elimination potential of the liver and kidneys. However, the older patient group are a heterogeneous population. The available data on treatment of older patients with CRC indicate that fit older adult patients have the potential to derive the same benefit as do younger patients. A comprehensive geriatric assessment can help to identify patients most likely to benefit from standard treatment. In this review, we will evaluate the chemotherapy regimens investigated in older adult patients with CRC, and how the safety profiles and efficacy of chemotherapy in the older adult compare with those observed in younger patients.
Collapse
Affiliation(s)
- Muhammad W Saif
- Yale University School of Medicine, Section of Medical Oncology, 333 Cedar Street, FMP 116, New Haven, CT 06520, USA.
| | | |
Collapse
|
|
34
|
Feliu J, Sereno M, Castro JD, Belda C, Casado E, González-Barón M. Chemotherapy for colorectal cancer in the elderly: Whom to treat and what to use. Cancer Treat Rev 2009; 35:246-54. [PMID: 19345021 DOI: 10.1016/j.ctrv.2008.11.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2008] [Revised: 11/13/2008] [Accepted: 11/17/2008] [Indexed: 12/27/2022]
Abstract
The median age at diagnosis of colorectal cancer is during the seventh decade, and the incidence of the disease increases continuously with age. However, as the age increases, the possibilities of receiving adequate cancer treatment diminish and the mortality rises. So, there is a huge need for defined treatment strategies in elderly patients with colorectal carcinoma. The geriatric population is a very heterogeneous group where patients with an excellent health status coexist with the patients with both co-morbidities and functional dependency. Therefore, it is necessary to personalize each treatment according to the degree of vulnerability of the elderly patients. It is essential to set up a multidimensional geriatric assessment in order to consider not only the stage of the disease, but also all the factors that may influence the survival and interfere with the treatment. The aim of this review is to discuss the potential benefits and issues of chemotherapy in the elderly patients affected with colorectal cancer.
Collapse
Affiliation(s)
- Jaime Feliu
- Medical Oncology Department, La Paz Hospital, Madrid, Spain
| | | | | | | | | | | |
Collapse
|
|
35
|
Merlin F, Prochilo T, Tondulli L, Kildani B, Beretta GD. Colorectal cancer treatment in elderly patients: an update on recent clinical studies. Clin Colorectal Cancer 2009; 7:357-63. [PMID: 19036687 DOI: 10.3816/ccc.2008.n.047] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Colorectal cancer (CRC) is one of the most common cancers in the Western world, with > 500,000 new cases diagnosed each year. One of the strongest risk factors for colon cancer is age. Physicians and their older patients commonly face the dilemma of whether to give/receive systemic chemotherapy for CRC. Evidence supports similar survival benefits with adjuvant and palliative chemotherapy in elderly patients compared with younger age groups. Data on treatment- related side effects did not reveal a different toxicity profile for elderly patients. The safety and efficacy of systemic chemotherapy in fit older patients were proven, and this group of patients could be enrolled in clinical trials. Conversely, frail older patients are more likely to suffer adverse outcomes when faced with stressors and might not benefit from chemotherapy. Despite a growing body of data, a great deal of work is still needed to establish optimal strategies to care for patients diagnosed with cancer later in life. There is a paucity of reports published in the literature because of the difficulty in routinely collecting such data. We report an overview of recent studies (clinical trials, pooled analysis, and population studies) to provide more information and to identify new and better treatment options.
Collapse
Affiliation(s)
- Federica Merlin
- U.O.Oncologia Medica, Ospedale Sant'Orsola Fatebenefratelli, via Vittorio Emanuele II, Brescia, Italy
| | | | | | | | | |
Collapse
|
|
36
|
Power DG, Lichtman SM. Adjuvant and Palliative Chemotherapy for Colon Cancer in the Elderly Patient. SEMINARS IN COLON AND RECTAL SURGERY 2008. [DOI: 10.1053/j.scrs.2008.09.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
|
|
37
|
Kweekel D, Guchelaar HJ, Gelderblom H. Clinical and pharmacogenetic factors associated with irinotecan toxicity. Cancer Treat Rev 2008; 34:656-69. [DOI: 10.1016/j.ctrv.2008.05.002] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2008] [Revised: 04/29/2008] [Accepted: 05/02/2008] [Indexed: 01/26/2023]
|
|
38
|
Köhne CH, Folprecht G, Goldberg RM, Mitry E, Rougier P. Chemotherapy in elderly patients with colorectal cancer. Oncologist 2008; 13:390-402. [PMID: 18448553 DOI: 10.1634/theoncologist.2007-0043] [Citation(s) in RCA: 82] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Significant advancements in chemotherapy for metastatic colorectal cancer (mCRC) have been achieved over the past decade, and the median overall survival duration is now close to 24 months with appropriate treatment. The most widely recommended chemotherapy regimens are based on the use of irinotecan or oxaliplatin in combination with 5-fluorouracil and leucovorin; some data suggest further benefit with the addition of the targeted agents bevacizumab or cetuximab. Colorectal cancer primarily affects the elderly; however, much of the defining clinical research in this field has excluded subjects of advanced age or with a poor performance status, making it difficult for clinicians to interpret current treatment paradigms for their older patients. Most clinical trials that have included elderly patients document similar survival rates and toxicity profiles to those seen in younger patients. Moreover, survey data suggest that >70% of elderly patients with cancer are willing to undergo strong, palliative chemotherapy. While these findings suggest that age itself should not determine candidacy for chemotherapy, it is important to note the great heterogeneity of the elderly population with regard to overall health, independence, and performance status. The use of a comprehensive geriatric assessment is recommended to evaluate chemotherapy appropriateness. The management of frail elderly patients and those with a short life expectancy should be focused on palliation, while fit elderly patients can receive aggressive therapy in a similar fashion to younger patients.
Collapse
Affiliation(s)
- Claus-Henning Köhne
- Klinik für Onkologie/Hämatologie, Klinikum Oldenburg, Dr.-Eden-Str. 10, 26133 Oldenburg, Germany.
| | | | | | | | | |
Collapse
|
|
39
|
Irinotecan in the treatment of elderly patients with advanced colorectal cancer. Crit Rev Oncol Hematol 2008; 68:250-5. [PMID: 18722784 DOI: 10.1016/j.critrevonc.2008.05.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2008] [Revised: 05/26/2008] [Accepted: 05/30/2008] [Indexed: 01/03/2023] Open
Abstract
UNLABELLED Irinotecan is an active drug in the first and subsequent lines of chemotherapy for patients with advanced colorectal cancer. Frequently, the elderly patients are excluded from receiving irinotecan alone or in combination, and on many occasions these patients receive an initial reduced dose of this drug. This revision has been focused in the role of irinotecan in elderly patients. MATERIAL AND METHODS Data from pharmacokinetic studies, comparative analysis of prospective trials according to age and prospective studies with irinotecan alone or irinotecan-combinations in the elderly have been revised and put into context. RESULTS Either pharmacokinetic and clinical data suggest that fit elderly patients may tolerate irinotecan as well as the younger population. Response rate and survival achieved in elderly patients with irinotecan combinations seem to be equivalent to that obtained in younger patients. CONCLUSION Elderly patients with advanced colorectal cancer should be carefully evaluated in order to be classified as fit or not fit through a comprehensive geriatric assessment. For the group of fit elderly patients, irinotecan may be used as in the younger population.
Collapse
|
|
40
|
Rosati G, Bilancia D. Role of chemotherapy and novel biological agents in the treatment of elderly patients with colorectal cancer. World J Gastroenterol 2008; 14:1812-22. [PMID: 18350617 PMCID: PMC2699600 DOI: 10.3748/wjg.14.1812] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2007] [Revised: 12/15/2008] [Indexed: 02/06/2023] Open
Abstract
Patients older than 65 years are the fastest growing segment of the cancer population. It is estimated that within 20 years over 75% of cases and 85% of deaths from colorectal cancer (CRC) will be in this setting. Concerns about cancer treatment in the elderly relate to comorbidities, which increase proportionally with age, physiological changes associated with aging which may influence drug metabolism and toxicity, and diminishing life expectancy, which particularly impacts decisions surrounding the benefits of adjuvant therapies. Over the last 10 years, significant improvements in the treatment of advanced CRC with combination therapy have been made. The randomized trials which have defined these improvements did not exclude elderly patients. However, the median age of patients in these trials has generally been approximately 60 years. Thus, it appears that some degree of selection is involved with younger and presumably fitter patients being the subjects in most of the pivotal trials. The availability of new molecularly targeted agents and newly improved existing agents has expanded the range of treatment options available. This variety gives greater flexibility in dealing with different subsets of patients, such as the elderly. However, some fit elderly patients seem to tolerate combination therapy reasonably well, while studies on unfit elderly subjects are needed.
Collapse
|
|
41
|
Folprecht G, Seymour MT, Saltz L, Douillard JY, Hecker H, Stephens RJ, Maughan TS, Van Cutsem E, Rougier P, Mitry E, Schubert U, Köhne CH. Irinotecan/fluorouracil combination in first-line therapy of older and younger patients with metastatic colorectal cancer: combined analysis of 2,691 patients in randomized controlled trials. J Clin Oncol 2008; 26:1443-51. [PMID: 18349394 DOI: 10.1200/jco.2007.14.0509] [Citation(s) in RCA: 168] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/30/2025] Open
Abstract
PURPOSE Uncertainty exists about whether elderly patients benefit to the same extent as younger patients from combination therapy with irinotecan in the first-line treatment of metastatic colorectal cancer (CRC). PATIENTS AND METHODS Combined analysis was carried out with source data from the fluorouracil (FU)/folinic acid (FA) and the irinotecan/FU/FA arms of four first-line, phase III trials of CRC to investigate the efficacy and safety of combination and monotherapy in elderly (age > or = 70 years; n = 599) compared with younger (age < 70 years; n = 2,092) patients. RESULTS Response rates were improved with irinotecan-based combination therapy compared with FU/FA in patients both younger than 70 years and > or = 70 years (46.6% v 29.0% P < .0001; and 50.5% v 30.3%, P < .0001, respectively). With irinotecan/FU/FA, progression-free survival was better for both younger (hazard ratio [HR], 0.77; 95% CI, 0.70 to 0.85; P < .0001) and elderly patients (HR, 0.75; 95% CI, 0.61 to 0.90; P = .0026). In younger patients, overall survival was improved with combination therapy (HR, 0.83; 95% CI, 0.75 to 0.92; P = .0003). The same trend was observed in elderly patients (HR, 0.87; 95% CI, 0.72 to 1.05; P = .15). There was no significant interaction between treatment arm and age in the regression analysis. The expected differences in toxicity between combination and monotherapy in elderly and younger patients were observed. A significant interaction between treatment and age (cutoff, 70 years) for vomiting and hepatotoxicity was not confirmed by analysis that used age as a continuous variable. CONCLUSION Patients older than 70 years of age who were selected for inclusion in phase III trials derived similar benefits as younger patients from irinotecan-containing chemotherapy, and the risk of toxicity was similar.
Collapse
Affiliation(s)
- Gunnar Folprecht
- University Hospital Dresden, Fetscherstr 74, Dresden, Germany 01307.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
42
|
Uedo N, Narahara H, Ishihara R, Takiuchi H, Goto M, Fujitani K, Hirao M, Tsujinaka T, Imano M, Furukawa H, Tsukuma H, Taguchi T. Phase II study of a combination of irinotecan and S-1 in patients with advanced gastric cancer (OGSG0002). Oncology 2008; 73:65-71. [PMID: 18334851 DOI: 10.1159/000120630] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2007] [Accepted: 09/04/2007] [Indexed: 01/26/2023]
Abstract
BACKGROUND/AIMS To investigate the efficacy and safety of the combination therapy of irinotecan (CPT-11) plus S-1 in patients with advanced gastric cancer at the dose recommended by a previous phase I study. METHODS A total of 23 patients received 80 mg/m(2) of CPT-11 on days 1 and 15, and S-1 at a dose level set on the basis of the body surface area (BSA): 40 (BSA <1.25 m(2)), 50 (BSA > or =1.25 to <1.5 m(2)) or 60 mg (BSA > or =1.5 m(2)) b.i.d. was given from days 1-21. RESULTS The overall response rate was 47.8% (11 of 23, 95% confidence interval, CI: 27.4-68.2%). The median time to progression (TTP) was 210 days (95% CI: 145-322 days) and the median survival time was 394 days (95% CI: 241-484 days). The incidence of grade 3 or 4 hematological and non-hematological toxicity was 17.4 and 8.7%. The most common hematological toxicity was anemia and the most common non-hematological toxicity was diarrhea. CONCLUSION The combination therapy of CPT-11 and S-1 provided prolonged TTP with low toxicity, and the results warrant a further phase III study to define the efficacy in improvement of survival in patients with advanced gastric cancer.
Collapse
Affiliation(s)
- Noriya Uedo
- Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka,
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
43
|
François E, Berdah JF, Chamorey E, Lesbats G, Teissier E, Codoul JF, Badetti JL, Hébert C, Mari V. Use of the folinic acid/5-fluorouracil/irinotecan (FOLFIRI 1) regimen in elderly patients as a first-line treatment for metastatic colorectal cancer: a Phase II study. Cancer Chemother Pharmacol 2008; 62:931-6. [DOI: 10.1007/s00280-008-0681-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2007] [Accepted: 01/07/2008] [Indexed: 10/22/2022]
|
|
44
|
Arkenau HT, Chua YJ, Cunningham D. Current treatment strategies in elderly patients with metastatic colorectal cancer. Clin Colorectal Cancer 2007; 6:508-15. [PMID: 17553199 DOI: 10.3816/ccc.2007.n.016] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Colorectal cancer (CRC) is one of the most common cancers in the Western world, with > 500,000 new cases diagnosed each year. One of the strongest risk factors for colon cancer is age. The incidence rates rise from 10 in 100,000 at age 40-45 years to 300 in 100,000 at age 75-80 years, with the median age at diagnosis of CRC being 71 years. With the general demographic shift toward an aging population, the number of people aged > 65 years is expected to increase. This article reviews the development of treatment for elderly patients with metastatic CRC, from single-agent fluoropyrimidines to combination therapies.
Collapse
Affiliation(s)
- Hendrik-Tobias Arkenau
- Department of Medical Oncology, Royal Marsden Hospital-London and Sutton, Surrey, United Kingdom
| | | | | |
Collapse
|
|
45
|
Abstract
Colorectal cancer (CRC) is predominantly a disease of older persons, and our population is aging. Physicians and their older patients commonly face the dilemma of whether or not to give/receive systemic chemotherapy for CRC. Evidence supports the safety and efficacy of systemic chemotherapy in fit older patients motivated enough to enroll onto clinical trials. Conversely, frail older patients are more likely to suffer adverse outcomes when faced with stressors and may not benefit from chemotherapy. However, the majority of patients are neither fit nor frail, and current evidence is insufficient to either quantify or qualify the benefit of chemotherapy for this intermediate group of patients. Thus, treatment decisions must be individualized based on each older person's physical state (eg, their function and degree of comorbidity) and values. Despite a growing body of data, a great deal of work is still needed to establish optimal strategies to care for patients diagnosed with cancer later in life.
Collapse
Affiliation(s)
- Hanna Kelly Sanoff
- Department of Medicine, Division of Hematology-Oncology, University of North Carolina at Chapel Hill, NC 27599, USA
| | | | | |
Collapse
|
|
46
|
Lichtman SM, Wildiers H, Chatelut E, Steer C, Budman D, Morrison VA, Tranchand B, Shapira I, Aapro M. International Society of Geriatric Oncology Chemotherapy Taskforce: evaluation of chemotherapy in older patients--an analysis of the medical literature. J Clin Oncol 2007; 25:1832-43. [PMID: 17488981 DOI: 10.1200/jco.2007.10.6583] [Citation(s) in RCA: 153] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
The elderly comprise the majority of patients with cancer and are the recipients of the greatest amount of chemotherapy. Unfortunately, there is a lack of data to make evidence-based decisions with regard to chemotherapy. This is due to the minimal participation of older patients in clinical trials and that trials have not systematically evaluated chemotherapy. This article reviews the available information with regard to chemotherapy and aging provided by a task force of the International Society of Geriatric Oncology (SIOG). Due to the lack of prospective data, the conclusions and recommendations made are a consensus of the participants. Extrapolation of data from younger to older patients is necessary, particularly to those patients older than 80 years, for which data is almost entirely lacking. The classes of drugs reviewed include alkylators, antimetabolites, anthracyclines, taxanes, camptothecins, and epipodophyllotoxins. Clinical trials need to incorporate an analysis of chemotherapy in terms of the pharmacokinetic and pharmacodynamic effects of aging. In addition, data already accumulated need to be reanalyzed by age to aid in the management of the older cancer patient.
Collapse
Affiliation(s)
- Stuart M Lichtman
- Memorial Sloan-Kettering Cancer Center, Commack, New York 11725, USA.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
47
|
Reddy N, Yu J, Fakih MG. Toxicities and Survival Among Octogenarians and Nonagenarians with Colorectal Cancer Treated with Chemotherapy or Concurrent Chemoradiation Therapy. Clin Colorectal Cancer 2007; 6:362-6. [PMID: 17311701 DOI: 10.3816/ccc.2007.n.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
PURPOSE Patients aged > or = 70 years with colon cancer benefit from chemotherapy, with no major added toxicities compared with a younger population. However, the safety and efficacy of chemotherapy or chemoradiation therapy in octogenarians and nonagenarians with colorectal cancer (CRC) has not been previously reported. PATIENTS AND METHODS We conducted a retrospective study of the safety and efficacy of chemotherapy or chemoradiation therapy in patients with CRC treated between January 2002 and June 2006 at Roswell Park Cancer Institute. RESULTS Thirty-three patients were identified, 24 of whom had colon cancer and 9 of whom had rectal cancer. Twenty-two patients with metastatic colon cancer and 8 patients with rectal cancer were evaluable for toxicity. All patients were started on an attenuated regimen of chemotherapy. A high rate of severe diarrhea (46%) and treatment-related hospitalizations (73%) were noted among patients with metastatic colon cancer. Toxicities were managed by treatment interruptions. The median overall survival among the metastatic colon cancer cohort was 20.6 months (95% confidence interval, 11.1-26.4 months). Among the patients with rectal cancer, 5 had locally advanced disease and were treated with chemoradiation therapy. Chemotherapy was interrupted in 3 of 5 patients because of toxicity. Radiation therapy was discontinued because of toxicity in 1 of 5 patients. CONCLUSION Our results suggest the susceptibility of patients with CRC aged > or = 80 years to chemotherapy toxicity. This age group should receive an attenuated dose of chemotherapy and be evaluated for dedicated clinical trials. Despite the high rate of treatment toxicity, selected octogenarians and nonagenarians with advanced CRC could benefit from chemotherapy, with overall survival neighboring that seen in younger populations.
Collapse
Affiliation(s)
- Nishitha Reddy
- Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
| | | | | |
Collapse
|
|
48
|
Souglakos J, Androulakis N, Syrigos K, Polyzos A, Ziras N, Athanasiadis A, Kakolyris S, Tsousis S, Kouroussis C, Vamvakas L, Kalykaki A, Samonis G, Mavroudis D, Georgoulias V. FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG). Br J Cancer 2006; 94:798-805. [PMID: 16508637 PMCID: PMC2361370 DOI: 10.1038/sj.bjc.6603011] [Citation(s) in RCA: 278] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2005] [Revised: 01/19/2006] [Accepted: 01/23/2006] [Indexed: 11/09/2022] Open
Abstract
To compare the efficacy and toxicity of oxaliplatin (L-OHP) in combination with irinotecan (CPT-11), 5-fluorouracil (5-FU) and leucovorin (LV) (FOLFOXIRI) vs irinotecan and 5-FU/LV (FOLFIRI) as first-line treatment of patients with metastatic colorectal cancer (MCC). A total of 283 chemotherapy-naïve patients with MCC were enrolled (FOLFIRI arm: n=146; FOLFOXIRI arm: n=137). In the FOLFOXIRI arm, CPT-11 (150 mg m(-2)) was given on d1, L-OHP (65 mg m(-2)) on d2, LV (200 mg m(-2)) on days 2 and 3 and 5-FU (400 mg m(-2) as i.v. bolus and 600 mg m(-2) as 22 h i.v. continuous infusion) on days 2 and 3. In the FOLFIRI arm, CPT-11 (180 mg m(-2)) was given on d1 whereas LV and 5-FU were administered in the same way as in the FOLFOXIRI regimen. Both regimens were administered every 2 weeks. There was no difference in terms of overall survival (median OS: 19.5 and 21.5 months, for FOLFIRI and FOLFOXIRI, respectively; P=0.337), median time to disease progression (FOLFIRI: 6.9 and FOLFOXIRI: 8.4 months; P=0.17), response rates (33.6 and 43% for FOLFIRI and FOLFOXIRI, respectively; P=0.168). Patients treated with FOLFOXIRI had a significantly higher incidence of alopecia (P=0.0001), diarrhoea (P=0.0001) and neurosensory toxicity (P=0.001) compared with patients treated with FOLFIRI. The present study failed to demonstrate any superiority of the FOLFOXIRI combination compared with the FOLFIRI regimen, although the observed median OS is one of the best ever reported in the literature.
Collapse
Affiliation(s)
- J Souglakos
- Department of Medical Oncology, University General Hospital of Heraklion, PO Box 1352, Heraklion, Crete 71110, Greece.
| | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|