|
1
|
Van der Speeten K, Kusamura S, Villeneuve L, Piso P, Verwaal VJ, González-Moreno S, Glehen O. The 2022 PSOGI International Consensus on HIPEC Regimens for Peritoneal Malignancies: HIPEC Technologies. Ann Surg Oncol 2024; 31:7090-7110. [PMID: 39037523 DOI: 10.1245/s10434-024-15513-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 05/09/2024] [Indexed: 07/23/2024]
Abstract
This manuscript reports the results of an international consensus on technologies of hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) performed with the following goals: To provide recommendations for the technological parameters to perform HIPEC. To identify the role of heat and its application forms in treating peritoneal metastases. To provide recommendations regarding the correct dosimetry of intraperitoneal chemotherapy drugs and their carrier solutions. To identify for each intraperitoneal chemotherapy regimen the best dosimetry and fractionation. To identify areas of future research pertaining to HIPEC technology and regimens. This consensus was performed by the Delphi technique and comprised two rounds of voting. In total, 96 of 102 eligible panelists replied to both Delphi rounds (94.1%) with a consensus of 39/51 questions on HIPEC technical aspects. Among the recommendations that met with the strongest consensus were those concerning the dose of HIPEC drug established in mg/m2, a target temperature of at least 42°C, and the use of at least three temperature probes to pursue hyperthermia. Ninety minutes as the ideal HIPEC duration seemed to make consensus. These results should be considered when designing new clinical trials in patients with peritoneal surface malignancies.
Collapse
Affiliation(s)
- Kurt Van der Speeten
- Department of Surgical Oncology, Ziekenhuis Oost-Limburg, Genk, Belgium.
- Faculty of Life Sciences, BIOMED Research Institute, University Hasselt, Hasselt, Belgium.
| | - Shigeki Kusamura
- Department of Surgical Oncology, PSM unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Laurent Villeneuve
- Department of Surgical Oncology, Centre Hospitalier Lyon-sud, Lyon, France
| | - Pompiliu Piso
- Department of General and Visceral Surgery, Hospital Barmherzige Brüder, Regensburg, Germany
| | - Vic J Verwaal
- Peritoneal Surface Malignancy and HIPEC Institute for Regional Sundhedforskning, Syddansk University, Odense, Sweden
| | | | - Olivier Glehen
- Department of Surgical Oncology, Centre Hospitalier Lyon-sud, Lyon, France
| |
Collapse
|
|
2
|
Wang Q, Liu H, Shen Y, Shen L, Li J, Feng W. The impact of Paclitaxel-based hyperthermic intraperitoneal chemotherapy in advanced high-grade serous ovarian cancer patients - interim analysis of safety and immediate efficacy of a randomized control trial (C-HOC trial). J Ovarian Res 2024; 17:145. [PMID: 38997720 PMCID: PMC11241942 DOI: 10.1186/s13048-024-01468-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Accepted: 06/29/2024] [Indexed: 07/14/2024] Open
Abstract
OBJECTIVE This study evaluates the potential superiority of combining paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) with sequential intravenous neoadjuvant chemotherapy over intravenous neoadjuvant chemotherapy alone in Chinese patients with Federation of Gynecology and Obstetrics (FIGO) stage IIIC, IVA and IVB high-grade serous ovarian/fallopian tube carcinoma (HGSOC). This interim analysis focuses on the safety and immediate efficacy of both regimens to determine the feasibility of the planned trial (C-HOC Trial). METHODS In a single-center, open-label, randomized control trial, FIGO stage IIIC, IVA, and IVB HGSOC patients (FAGOTTI score ≥ 8 during laparoscopic exploration) unsuitable for optimal cytoreduction in primary debulking surgery (PDS) were randomized 2:1 during laparoscopic exploration. The Experiment Group (HIPEC Group) received one cycle of intraperitoneal neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (paclitaxel) followed by three cycles of intravenous chemotherapy (paclitaxel plus carboplatin), while the Control Group received only three cycles of intravenous chemotherapy. Both groups subsequently underwent interval debulking surgery (IDS). The adverse effects of chemotherapy, postoperative complications, and pathological chemotherapy response scores (CRS) after IDS were compared. RESULTS Among 65 enrolled patients, 39 HIPEC Group and 21 Control Group patients underwent IDS. Grade 3-4 chemotherapy-related adverse effects were primarily hematological with no significant differences between the two groups. The HIPEC Group exhibited a higher proportion of CRS 3 (20.5% vs. 4.8%; P = 0.000). R0 resection rates in IDS were 69.2% (HIPEC Group) and 66.7% (Control Group). R2 resection occurred in 2.6% (HIPEC Group) and 14.3% (Control Group) cases. No reoperations or postoperative deaths were reported, and complications were managed conservatively. CONCLUSIONS Combining HIPEC with IV NACT in treating ovarian cancer demonstrated safety and feasibility, with no increased chemotherapy-related adverse effects or postoperative complications. HIPEC improved tumor response to neoadjuvant chemotherapy, potentially enhancing progression-free survival (PFS). However, the final overall survival results are pending, determining if HIPEC combined with IV NACT is superior to IV NACT alone.
Collapse
Affiliation(s)
- Qun Wang
- Department of Gynecology and Obstetrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Hua Liu
- Department of Gynecology and Obstetrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuhong Shen
- Department of Gynecology and Obstetrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lifei Shen
- Department of Gynecology and Obstetrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jian Li
- Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiwei Feng
- Department of Gynecology and Obstetrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| |
Collapse
|
|
3
|
Villarejo Campos P, Sánchez García S, Amo-Salas M, García Santos E, López de la Manzanara C, Alberca A, Padilla-Valverde D, Redondo Calvo FJ, Martín J. Paclitaxel as HIPEC-Drug after Surgical Cytoreduction for Ovarian Peritoneal Metastases: A Randomized Phase III Clinical Trial (HIPECOVA). Curr Oncol 2024; 31:660-671. [PMID: 38392042 PMCID: PMC10888026 DOI: 10.3390/curroncol31020048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 01/13/2024] [Accepted: 01/22/2024] [Indexed: 02/24/2024] Open
Abstract
Multidisciplinary strategies have transformed the management of advanced ovarian cancer. We aimed to evaluate the effectiveness of paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical cytoreduction for ovarian peritoneal metastases in a randomized phase III trial conducted between August 2012 and December 2019. Seventy-six patients were randomized to either the HIPEC or no HIPEC group. Although median values for the primary endpoints (recurrence-free survival (RFS) and overall survival (OS)) revealed superior outcomes for the HIPEC (RFS: 23 months, OS: 48 months) over the control group (RFS: 19 months, OS: 46 months), these differences were not statistically significant (p = 0.22 and p = 0.579). Notably, the HIPEC group demonstrated significantly higher 5-year OS and 3-year RFS rates (47.2% and 47.5%) compared to patients without HIPEC (34.5% and 21.3%). Stratification according to Peritoneal Surface Disease Severity Score (PSDSS) showed improved OS and RFS for patients with lower PSDSS (I-II) in the HIPEC-treated group (p = 0.033 and p = 0.042, respectively). The Clavien-Dindo classification of adverse event grades revealed no significant differences between HIPEC and controls (p = 0.482). While overall results were not statistically significant, our long-term follow-up emphasized the potential benefit of HIPEC-associated cytoreduction with paclitaxel, particularly in selected ovarian cancer patients with lower PSDSS indices.
Collapse
Affiliation(s)
- Pedro Villarejo Campos
- Department of Surgery, Fundación Jiménez Díaz University Hospital, Avda. Reyes Católicos, 2, 28040 Madrid, Spain
- Department of Surgery, Universidad Autónoma de Madrid, C/Arzobispo Morcillo s/n, 28034 Madrid, Spain
| | - Susana Sánchez García
- Department of Surgery, General University Hospital of Ciudad Real, C/Obispo Rafael Torija, s/n, 13005 Ciudad Real, Spain; (S.S.G.); (E.G.S.); (D.P.-V.); (J.M.)
| | - Mariano Amo-Salas
- Department of Mathematics, University of Castilla-La Mancha, Camino de Moledores, s/n, 13071 Ciudad Real, Spain;
| | - Esther García Santos
- Department of Surgery, General University Hospital of Ciudad Real, C/Obispo Rafael Torija, s/n, 13005 Ciudad Real, Spain; (S.S.G.); (E.G.S.); (D.P.-V.); (J.M.)
| | - Carlos López de la Manzanara
- Department of Gynaecology, General University Hospital of Ciudad Real, C/Obispo Rafael Torija, s/n, 13005 Ciudad Real, Spain;
| | - Ana Alberca
- Department of Surgery, General University Hospital of Jaén, 23007 Jaén, Spain;
| | - David Padilla-Valverde
- Department of Surgery, General University Hospital of Ciudad Real, C/Obispo Rafael Torija, s/n, 13005 Ciudad Real, Spain; (S.S.G.); (E.G.S.); (D.P.-V.); (J.M.)
| | - Francisco Javier Redondo Calvo
- Department of Anaesthesia, General University Hospital of Ciudad Real, C/Obispo Rafael Torija, s/n, 13005 Ciudad Real, Spain;
| | - Jesús Martín
- Department of Surgery, General University Hospital of Ciudad Real, C/Obispo Rafael Torija, s/n, 13005 Ciudad Real, Spain; (S.S.G.); (E.G.S.); (D.P.-V.); (J.M.)
| |
Collapse
|
|
4
|
Buckarma E, Thiels CA, Jin Z, Grotz TE. Cytoreduction and Hyperthermic Intraperitoneal Paclitaxel and Cisplatin for Gastric Cancer with Peritoneal Metastasis. Ann Surg Oncol 2024; 31:622-629. [PMID: 37880514 DOI: 10.1245/s10434-023-14379-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 09/15/2023] [Indexed: 10/27/2023]
Abstract
BACKGROUND Peritoneal metastasis (PM) is the most common site of dissemination of gastric cancer (GC) and is associated with a poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for GC with PM remains controversial due to modest survival and significant morbidity. METHODS We conducted a retrospective analysis of patients with GC and PM treated with CRS and HIPEC with cisplatin and paclitaxel for 90 min from June 2019 to December 2022. RESULTS Twenty-two patients were included and received a median of 7 (interquartile range [IQR] 4-8) cycles of neoadjuvant systemic therapy. Seventeen patients (77%) underwent a single neoadjuvant laparoscopic HIPEC, and six (27%) patients received chemoradiation. The median Peritoneal Carcinomatosis Index at the time of CRS was 1 (IQR 0-4), and 21 patients (95%) underwent complete cytoreduction (CC-0). An R0 resection was achieved in 20 (91%) patients, and the median length of stay was 5.5 (IQR 4-7.5) days. There were six (27%) 90-day major complications (Clavien-Dindo grade ≥ 3), one (4%) Common Terminology Classification for Adverse Events (CTCAE) grade 4 cytopenia, and one (4%) acute kidney injury. The rate of anastomotic leak (all grades) was 14%, the 30-day readmission rate was 18%, and the 90-day mortality rate was 0%. At a median follow-up of 24 months, the median progression-free survival (PFS) and overall survival (OS) were not reached. The 1-, 2-, and 3-year PFS rates were 65%, 56%, and 40%, respectively, and the 1-, 2-, and 3-year OS rates were 96%, 78%, and 55%, respectively. CONCLUSIONS CRS and HIPEC with paclitaxel and cisplatin is well tolerated and is associated with favorable oncologic and perioperative outcomes.
Collapse
Affiliation(s)
- EeeLN Buckarma
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Cornelius A Thiels
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Zhaohui Jin
- GI Care Team, Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA
| | - Travis E Grotz
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA.
| |
Collapse
|
|
5
|
Bhatt A, Glehen O, Zivanovic O, Brennan D, Nadeau C, Van Driel W, Bakrin N. The 2022 PSOGI International Consensus on HIPEC Regimens for Peritoneal Malignancies: Epithelial Ovarian Cancer. Ann Surg Oncol 2023; 30:8115-8137. [PMID: 37561343 DOI: 10.1245/s10434-023-13932-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 06/27/2023] [Indexed: 08/11/2023]
Abstract
BACKGROUND AND AIM We report the results of an international consensus on hyperthermic intraperitoneal chemotherapy (HIPEC) regimens for epithelial ovarian cancer (EOC) performed with the following goals: To define the indications for HIPEC To identify the most suitable HIPEC regimens for each indication in EOC To identify areas of future research on HIPEC To provide recommendations for some aspects of perioperative care for HIPEC METHODS: The Delphi technique was used with two rounds of voting. There were three categories of questions: evidence-based recommendations [using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system with the patient, intervention, comparator, and outcome (PICO) method], an opinion survey, and research recommendations. RESULTS Seventy-three (67.5%) of 108 invited experts responded in round I, and 68 (62.9%) in round II. Consensus was achieved for 34/38 (94.7%) questions. However, a strong positive consensus that would lead to inclusion in routine care was reached for only 6/38 (15.7%) questions. HIPEC in addition to interval cytoreductive surgery (CRS) received a strong positive recommendation that merits inclusion in routine care. Single-agent cisplatin was the only drug recommended for routine care, and OVHIPEC-1 was the most preferred regimen. The panel recommended performing HIPEC for a minimum of 60 min with a recommended minimum intraabdominal temperature of 41°C. Nephroprotection with sodium thiosulfate should be used for cisplatin HIPEC. CONCLUSIONS The results of this consensus should guide clinical decisions on indications of HIPEC and the choice and various parameters of HIPEC regimens and could fill current knowledge gaps. These outcomes should be the basis for designing future clinical trials on HIPEC in EOC.
Collapse
Affiliation(s)
- Aditi Bhatt
- Department of Surgical Oncology, KD Hospital, Ahmedabad, India.
| | - Olivier Glehen
- Department of Surgical Oncology, Centre Hospitalier, Lyon-sud, Lyon, France
| | - Oliver Zivanovic
- Department of Gynecological Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Donal Brennan
- UCD Gynaecological Oncology Group, UCD School of Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Cedric Nadeau
- Department of Gynecological Oncology, CHU de Poitiers, Poitiers, Cedex, France
| | - Willemien Van Driel
- Department of Gynecological Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Naoual Bakrin
- Department of Surgical Oncology, Centre Hospitalier, Lyon-sud, Lyon, France
| |
Collapse
|
|
6
|
Yoo JG, Kim JH, Park EY, Kim I, Lim MC, Lee SJ. Ten-year treatment outcomes of consolidation hyperthermic intraperitoneal chemotherapy for ovarian cancer (HIPEC-KOV-03R). J Gynecol Oncol 2023; 34:e72. [PMID: 37417300 PMCID: PMC10627752 DOI: 10.3802/jgo.2023.34.e72] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 04/18/2023] [Accepted: 05/13/2023] [Indexed: 07/08/2023] Open
Abstract
OBJECTIVE We aimed to evaluate the long-term efficacy of consolidation hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with primary epithelial ovarian cancer. METHODS This retrospective cohort study included patients who underwent second-look surgery either with or without HIPEC after having complete or partial response to primary cytoreductive surgery and adjuvant platinum-based chemotherapy between January 1991 and December 2003 at Seoul St. Mary's Hospital. The 10-year progression-free survival (PFS), overall survival (OS), and toxicity within postoperative 28 days were investigated. RESULTS A total of 87 patients were identified, 44 (50.6%) received second-look surgery with HIPEC whereas 43 (49.4%) received only second-look surgery. The 10-year PFS and OS were significantly longer in the HIPEC group compared with the control group (PFS, 53.6% vs. 34.9%, log-rank p=0.009; OS, 57.0% vs. 34.5%, log-rank p=0.025). Multivariable analysis identified HIPEC as an independent favorable prognostic factor for PFS (adjusted hazard ratio [HR]=0.42; 95% confidence interval [CI]=0.23-0.77; p=0.005) but not for OS (adjusted HR=0.58; 95% CI=0.32-1.07; p=0.079). The more common adverse events in the HIPEC group were thrombocytopenia (90.9% vs. 68.3%, p=0.005), elevated liver enzymes (65.9% vs. 29.3%, p=0.002), and wound complications (18.2% vs. 2.4%, p=0.032). However, these adverse events were reversible and did not delay subsequent consolidation chemotherapy. CONCLUSION The consolidation HIPEC demonstrated a significant improvement in 10-year PFS but not OS, with acceptable toxicity in patients with primary epithelial ovarian cancer. Further randomized controlled trials are warranted to confirm these results.
Collapse
Affiliation(s)
- Ji Geun Yoo
- Department of Obstetrics and Gynecology, Daejeon St. Mary's Hospital, The Catholic University of Korea, Daejeon, Korea
| | - Ji Hyun Kim
- Center for Gynecologic Cancer, National Cancer Center, Goyang, Korea
| | - Eun Young Park
- Biostatistics Collaboration Team, Research Core Center, National Cancer Center, Goyang, Korea
| | - Imhyeon Kim
- Department of Obstetrics and Gynecology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
| | - Myong Cheol Lim
- Center for Gynecologic Cancer, National Cancer Center, Goyang, Korea.
| | - Sung Jong Lee
- Department of Obstetrics and Gynecology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
| |
Collapse
|
|
7
|
Grotz TE, Yonkus JA, Thiels CA, Warner SG, McWilliams RR, Mahipal A, Bekaii-Saab TS, Cleary SP, Kendrick ML, Truty MJ. Cytoreduction with Hyperthermic Intraperitoneal Chemoperfusion for Pancreatic Cancer with Low-Volume Peritoneal Metastasis: Results from a Prospective Pilot Study. Ann Surg Oncol 2023; 30:395-403. [PMID: 35972667 DOI: 10.1245/s10434-022-12328-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 07/12/2022] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Resection of oligometastatic pancreatic ductal adenocarcinoma (PDAC) has historically been ineffective, however modern systemic chemotherapy has improved survival. Thus, re-evaluating safety and outcomes of surgical resection in selected patients with limited peritoneal metastasis (PM) warrants consideration. METHODS From 2018 to 2021, patients with PDAC and positive cytology or limited PM without extraperitoneal metastasis and who had an objective response to ≥ 6 months of systemic chemotherapy were enrolled. Patients underwent laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin/mitomycin C. If amenable to a complete cytoreduction, patients went on to cytoreduction and HIPEC. RESULTS Overall, 18 patients were enrolled and received a median of 14 (interquartile range [IQR] 12-17) cycles of chemotherapy; 16 (89%) patients received chemoradiation. Laparoscopic HIPEC was completed in 17 patients, with a median length of stay of 1 day, and no grade III complications or hematological toxicities were observed. All 18 patients subsequently underwent a complete cytoreduction (CC-0) along with definitive treatment of the primary tumor, with formal resection (7/18), irreversible electroporation (IRE; 10/18), or intraoperative radiation therapy (IORT; 1/18). Median PCI was 2 (IQR 0-4), median LOS was 7 days (IQR 6-8), and 7 (39%) patients were readmitted. Eight (44%) patients experienced grade 3 or higher complications, including one 30-day mortality. At a median follow-up of 16 months, the median progression-free survival was 20 months and the median overall survival was 26 months. CONCLUSION Cytoreduction and HIPEC for selected patients with low-volume PM from PDAC is safe and feasible with favorable short-term outcomes. A phase II trial (NCT04858009) is now enrolling to further assess this multimodality approach in select patients.
Collapse
Affiliation(s)
- Travis E Grotz
- Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA.
| | - Jennifer A Yonkus
- Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Cornelius A Thiels
- Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Susanne G Warner
- Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA
| | | | - Amit Mahipal
- Department of Medical Oncology, Mayo Clinic Rochester, Rochester, MN, USA
| | | | - Sean P Cleary
- Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Michael L Kendrick
- Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Mark J Truty
- Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA
| |
Collapse
|
|
8
|
Mehta S, Kammar P, Patel A, Goswami G, Shaikh S, Sukumar V, Trivedi E, Bhatt A. Feasibility and Safety of Taxane-PIPAC in Patients with Peritoneal Malignancies-a Retrospective Bi-institutional Study. Indian J Surg Oncol 2022; 14:1-9. [PMID: 36091624 PMCID: PMC9451111 DOI: 10.1007/s13193-022-01641-4] [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: 07/19/2022] [Accepted: 08/31/2022] [Indexed: 11/30/2022] Open
Abstract
Taxanes have a favorable pharmacokinetic profile for intraperitoneal application. We report our initial experience with taxane-PIPAC (pressurized intraperitoneal chemotherapy) for unresectable peritoneal metastases from different primary sites in terms of safety, feasibility, response rate, and conversion to resectability. In this retrospective study, PIPAC was performed alone or in combination with systemic chemotherapy. Paclitaxel was used as a single agent, whereas docetaxel was used in combination with cisplatin-adriamycin or oxaliplatin-adriamycin. From December 2019 to December 2021, 47 patients underwent 82 PIPAC procedures (1 PIPAC in 55.3%, 2 in 29.7%, 3 in 14.8%). The most common primary sites were ovarian cancer (31.9%), gastric cancer (23.4%), and colorectal cancer (21.2%). Docetaxel-cisplatin-adriamycin was used in 33 (70.2%) patients, docetaxel-oxaliplatin-adriamycin in 12 (25.5%), and paclitaxel alone in 2 (4.2%) patients. Grade 1-2 complications were observed in 24 (51%) and grade 3-4 complications in 6 (12.7%) patients (8.5% of 82 PIPACs). 16/47 (34.0%) patients had a clinical response to PIPAC. The mean PCI was 25.9 ± 9.2 for the first PIPACs and 22.4 ± 9 for the subsequent PIPACs with an average reduction of 3.6 points [change in PCI ranged from - 14 to + 8]. The PRGS was 1/2 in 4/47 (8.5%) patients (19.0% patients with > 1 PIPAC). A reduction in ascites was observed in 35.4% presenting with ascites. Nine (19.1%) patients had conversion to operability leading to a subsequent cytoreductive surgery in 8 (17%) patients. PIPAC with docetaxel is feasible and safe. The role of PIPAC with both docetaxel and paclitaxel either alone or in combination with other drugs should be investigated in prospective studies.
Collapse
Affiliation(s)
- Sanket Mehta
- Department of Surgical Oncology, Saifee Hospital, Mumbai, India
| | - Praveen Kammar
- Department of Surgical Oncology, Saifee Hospital, Mumbai, India
| | - Ankita Patel
- Department of Surgical Oncology, Zydus Hospital, Thaltej, Ahmedabad, 380054 India
| | - Gaurav Goswami
- Department of Radiology, Zydus Hospital, Ahmedabad, India
| | - Sakina Shaikh
- Department of Surgical Oncology, Zydus Hospital, Thaltej, Ahmedabad, 380054 India
| | - Vivek Sukumar
- Department of Surgical Oncology, Saifee Hospital, Mumbai, India
| | - Esha Trivedi
- Department of Surgical Oncology, Saifee Hospital, Mumbai, India
| | - Aditi Bhatt
- Department of Surgical Oncology, Zydus Hospital, Thaltej, Ahmedabad, 380054 India
| |
Collapse
|
|
9
|
Moukarzel LA, Ferrando L, Dopeso H, Stylianou A, Basili T, Pareja F, Da Cruz Paula A, Zoppoli G, Abu-Rustum NR, Reis-Filho JS, Long Roche K, Tew WP, Chi DS, Sonoda Y, Zamarin D, Aghajanian C, O'Cearbhaill RE, Zivanovic O, Weigelt B. Hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin induces distinct transcriptomic changes in ovarian tumor and normal tissues. Gynecol Oncol 2022; 165:239-247. [PMID: 35292180 PMCID: PMC9064951 DOI: 10.1016/j.ygyno.2022.02.022] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 02/23/2022] [Accepted: 02/27/2022] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To determine the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin on the transcriptomic profiles of normal and ovarian cancer (OC) tissues. METHODS Normal and tumor samples from four OCs were prospectively collected pre- and immediately post-HIPEC treatment and subjected to RNA-sequencing. Differential gene expression, gene ontology enrichment and pathway analyses were performed. Heat shock protein and immune-response protein expression was assessed using protein arrays and western blotting. RESULTS RNA-sequencing revealed 4231 and 322 genes significantly differentially expressed between pre- and post-treatment normal and OC tissues, respectively (both adjusted p-value <0.05). Gene enrichment analyses demonstrated that the most significantly upregulated genes in normal tissues played a role in immune as well as heat shock response (both adjusted p < 0.001). In contrast, HIPEC induced an increased expression of primarily heat shock response and protein folding-related genes in tumor tissues (both adjusted p < 0.001). HIPEC-induced heat shock protein (HSP) expression changes, including in HSP90, HSP40, HSP60, and HSP70, were also observed at the protein level in both normal and tumor tissues. CONCLUSIONS HIPEC with carboplatin resulted in an upregulation of heat shock-related genes in both normal and tumor tissue, with an additional immune response gene induction in normal and protein folding in tumor tissue. The findings of our exploratory study provide evidence to suggest that HIPEC administration may suffice to induce gene expression changes in residual tumor cells and raises a biological basis for the consideration of combinatorial treatments with HSP inhibitors.
Collapse
Affiliation(s)
- Lea A Moukarzel
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America
| | - Lorenzo Ferrando
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America; IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Higinio Dopeso
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America
| | - Anthe Stylianou
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America
| | - Thais Basili
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America
| | - Fresia Pareja
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America
| | - Arnaud Da Cruz Paula
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America
| | - Gabriele Zoppoli
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Nadeem R Abu-Rustum
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America
| | - Jorge S Reis-Filho
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America
| | - Kara Long Roche
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America
| | - William P Tew
- Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, United States of America
| | - Dennis S Chi
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America
| | - Yukio Sonoda
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America
| | - Dmitriy Zamarin
- Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, United States of America
| | - Carol Aghajanian
- Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, United States of America
| | - Roisin E O'Cearbhaill
- Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, United States of America; National University of Ireland, Galway, Ireland
| | - Oliver Zivanovic
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America
| | - Britta Weigelt
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America.
| |
Collapse
|
|
10
|
Vos LMC, Aronson SL, van Driel WJ, Huitema ADR, Schagen van Leeuwen JH, Lok CAR, Sonke GS. Translational and pharmacological principles of hyperthermic intraperitoneal chemotherapy for ovarian cancer. Best Pract Res Clin Obstet Gynaecol 2021; 78:86-102. [PMID: 34565676 DOI: 10.1016/j.bpobgyn.2021.06.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 06/09/2021] [Indexed: 12/24/2022]
Abstract
The long-term survival of advanced-stage ovarian cancer patients remains poor, despite extensive cytoreductive surgery, chemotherapy, and the recent addition of poly (ADP-ribose) polymerase inhibitors (PARPi). Hyperthermic intraperitoneal chemotherapy (HIPEC) has shown survival benefit by specifically targeting peritoneal metastases, the primary site of disease recurrence. Different aspects of how HIPEC exerts its effect remain poorly understood. Improved understanding of the effects of hyperthermia on ovarian cancer cells, the synergy of hyperthermia with intraperitoneal chemotherapy, and the pharmacological and pharmacokinetic properties of intraperitoneally administered cisplatin may help identify ways to optimize the efficacy of HIPEC. This review provides an overview of these translational and pharmacological principles of HIPEC and aims to expose knowledge gaps that may direct further research to optimize the HIPEC procedure and ultimately improve survival for women with advanced ovarian cancer.
Collapse
Affiliation(s)
- Laura M C Vos
- Dept. of Gynecologic Oncology, Center for Gynecologic Oncology, Amsterdam, Netherlands Cancer Institute, Amsterdam, the Netherlands.
| | - S Lot Aronson
- Dept. of Gynecologic Oncology, Center for Gynecologic Oncology, Amsterdam, Netherlands Cancer Institute, Amsterdam, the Netherlands; Dept. of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Willemien J van Driel
- Dept. of Gynecologic Oncology, Center for Gynecologic Oncology, Amsterdam, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Alwin D R Huitema
- Dept. of Pharmacology, Netherlands Cancer Institute, Amsterdam, the Netherlands; Dept. of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Dept. of Pharmacology, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
| | | | - Christine A R Lok
- Dept. of Gynecologic Oncology, Center for Gynecologic Oncology, Amsterdam, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Gabe S Sonke
- Dept. of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| |
Collapse
|
|
11
|
El Hajj H, Vanseymortier M, Hudry D, Bogart E, Abdeddaim C, Leblanc E, Le Deley MC, Narducci F. Rationale and study design of the CHIPPI-1808 trial: a phase III randomized clinical trial evaluating hyperthermic intraperitoneal chemotherapy (HIPEC) for stage III ovarian cancer patients treated with primary or interval cytoreductive surgery. ESMO Open 2021; 6:100098. [PMID: 33819750 PMCID: PMC8047490 DOI: 10.1016/j.esmoop.2021.100098] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 02/12/2021] [Accepted: 03/01/2021] [Indexed: 12/03/2022] Open
Abstract
Background Ovarian cancer remains the most lethal gynecologic malignancy with high recurrence rates. Because recurrence involves primarily the peritoneum, intraperitoneal chemotherapy is being evaluated as a new approach to treat microscopic peritoneal disease. One trial showed that cisplatin–paclitaxel intraperitoneal chemotherapy with intravenous paclitaxel improved survival but increased morbidity. Another trial reported a significant improvement in overall survival (OS) and disease-free survival (DFS) without increasing the morbidity (P = 0.76) or mortality rates (hazard ratio 0.67, P = 0.02) after adding hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreduction. The current trial aims to evaluate the impact of adding HIPEC to primary or interval cytoreductive surgery for epithelial ovarian cancer (EOC) on the efficacy, safety, treatment feasibility, and quality of life. Patients and methods This is an international, multicenter, open-label, randomized (1 : 1), two-arm, phase III clinical trial that will enroll 432 patients with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage III EOC. Patients are randomized to receive or not HIPEC with the standard of care. Inclusion criteria include patients with FIGO stage III EOC, Fallopian tube carcinoma or primary peritoneal cancer who undergo complete primary or interval cytoreduction. The primary objective is to assess DFS of the addition of HIPEC. Secondary objectives are the assessment of OS, safety, return to intended oncologic treatment, quality of life and the trade-off between efficacy and morbidity. Conclusions The results might help extend the indications of HIPEC to include patients undergoing primary cytoreduction, providing a standardized protocol for HIPEC in EOC management and reliable information on the quality of life after adding HIPEC.
Ovarian cancer remains the most lethal gynecologic cancer with high rates of recurrence involving primarily the peritoneum. Intraperitoneal chemotherapy is being evaluated as a new therapeutic approach to treat microscopic peritoneal disease. This trial evaluates the impact of adding HIPEC to primary or interval cytoreductive surgery for EOC. This trial evaluates the efficacy, safety, treatment feasibility and quality of life after the addition of HIPEC. This is an international, multicenter, open label, randomized, phase III clinical trial.
Collapse
Affiliation(s)
- Houssein El Hajj
- Gynecologic Oncology Department, Oscar Lambret Cancer Centre, Lille, France.
| | - M Vanseymortier
- Clinical Research and Innovation Department, Oscar Lambret Cancer Centre, Lille, France
| | - D Hudry
- Gynecologic Oncology Department, Oscar Lambret Cancer Centre, Lille, France
| | - E Bogart
- Clinical Research and Innovation Department, Oscar Lambret Cancer Centre, Lille, France
| | - C Abdeddaim
- Medical Oncology Department, Oscar Lambret Cancer Center, Lille, France
| | - E Leblanc
- Gynecologic Oncology Department, Oscar Lambret Cancer Centre, Lille, France
| | - M C Le Deley
- Paris-Saclay University, Paris-Sud University, UVSQ, CESP, INSERM, Villejuif, France
| | - F Narducci
- Gynecologic Oncology Department, Oscar Lambret Cancer Centre, Lille, France
| |
Collapse
|
|
12
|
Sugarbaker PH. Intraperitoneal paclitaxel: pharmacology, clinical results and future prospects. J Gastrointest Oncol 2021; 12:S231-S239. [PMID: 33968440 DOI: 10.21037/jgo-2020-03] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Paclitaxel administered into the peritoneal cavity is a chemotherapy agent that shows unusually prolonged retention within the peritoneal space. Using this pharmacokinetic fact as a starting point, the use of this drug to benefit patients with peritoneal metastases was investigated. The pharmacokinetics and drug characteristics of paclitaxel were identified from the oncologic literature. The experience to date with ovarian cancer, malignant peritoneal mesothelioma, gastric cancer and pancreas cancer was explored. Paclitaxel given by repeated instillation through an intraperitoneal port has demonstrable responses in ovarian cancer, peritoneal mesothelioma, gastric cancer and pancreas cancer when peritoneal metastases are present. Its role for prevention of peritoneal metastases in patients at high risk seems less well established. Randomized controlled studies have been positive in ovarian cancer but not in other diseases with peritoneal dissemination. A randomized controlled study in gastric cancer with peritoneal metastases produced suggestive but not conclusive results. Conversion surgery after repeated treatments with intraperitoneal paclitaxel has been reported with gastric cancer and pancreas cancer with peritoneal metastases. The pharmacology of intraperitoneal paclitaxel strongly suggest that intraperitoneal administration should be of benefit to prevent or treat peritoneal metastases. Protocols that the oncologist can follow to realize these potential benefits are not as yet available.
Collapse
Affiliation(s)
- Paul H Sugarbaker
- Center for Gastrointestinal Malignancies, MedStar Washington Hospital Center, Washington, DC, USA
| |
Collapse
|
|
13
|
de Bree E, Michelakis D. An overview and update of hyperthermic intraperitoneal chemotherapy in ovarian cancer. Expert Opin Pharmacother 2020; 21:1479-1492. [PMID: 32486865 DOI: 10.1080/14656566.2020.1766024] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Despite, the strong rationale and evidence of the benefit of postoperative intraperitoneal chemotherapy in advanced ovarian cancer, it has not been widely adopted, mainly due to its high morbidity and logistical difficulties. Intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is a more tolerable and technically feasible method of intraperitoneal chemotherapy, whereas other potential advantages include homogenous drug distribution, application before tumor regrowth and combination with hyperthermia, which is directly cytotoxic and enhances the efficacy of many drugs. AREAS COVERED In this review, the authors explain the rationale and indications for cytoreductive surgery (CRS) and HIPEC in advanced ovarian cancer. Data of major clinical studies, meta-analyses, and recent randomized trials are discussed. EXPERT OPINION After many encouraging clinical studies and meta-analyses, a recent randomized study demonstrated survival benefit for HIPEC during interval CRS in primary ovarian cancer, without increased morbidity, whereas another implied its benefit in recurrent ovarian cancer. Results of recently completed and numerous ongoing randomized studies will further determine the benefit of HIPEC in ovarian cancer at different time points. Patient selection and appraisal of the best protocols are crucial. The field of gynecological oncology will most likely evolve to include HIPEC eventually as a routine treatment for ovarian cancer.
Collapse
Affiliation(s)
- Eelco de Bree
- Department of Surgical Oncology, Medical School of Crete University Hospital , Heraklion, Greece
| | - Dimosthenis Michelakis
- Department of Surgical Oncology, Medical School of Crete University Hospital , Heraklion, Greece
| |
Collapse
|
|
14
|
Huang WC, Wu CC, Hsu YT, Chang CL. Effect of hyperthermia on improving neutrophil restoration after intraperitoneal chemotherapy. Int J Hyperthermia 2019; 36:1255-1263. [DOI: 10.1080/02656736.2019.1699172] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Affiliation(s)
- Wan-Chun Huang
- Department of Obstetrics and Gynecology, MacKay Memorial Hospital, Taipei City, Taiwan
| | - Chao-Chih Wu
- Department of Medical Research, MacKay Memorial Hospital, New Taipei City, Taiwan
| | - Yun-Ting Hsu
- Department of Medical Research, MacKay Memorial Hospital, New Taipei City, Taiwan
| | - Chih-Long Chang
- Department of Obstetrics and Gynecology, MacKay Memorial Hospital, Taipei City, Taiwan
- Department of Medical Research, MacKay Memorial Hospital, New Taipei City, Taiwan
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
| |
Collapse
|
|
15
|
Verco J, Johnston W, Frost M, Baltezor M, Kuehl PJ, Lopez A, Gigliotti A, Belinsky SA, Wolff R, diZerega G. Inhaled Submicron Particle Paclitaxel (NanoPac) Induces Tumor Regression and Immune Cell Infiltration in an Orthotopic Athymic Nude Rat Model of Non-Small Cell Lung Cancer. J Aerosol Med Pulm Drug Deliv 2019; 32:266-277. [PMID: 31347939 PMCID: PMC6781259 DOI: 10.1089/jamp.2018.1517] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background: This study evaluated the antineoplastic and immunostimulatory effects of inhaled (IH) submicron particle paclitaxel (NanoPac®) in an orthotopic non-small cell lung cancer rodent model. Methods: Male nude rats were whole body irradiated, intratracheally instilled with Calu-3 cancer cells and divided into six treatment arms (n = 20 each): no treatment (Group 1); intravenous nab-paclitaxel at 5.0 mg/kg once weekly for 3 weeks (Group 2); IH NanoPac at 0.5 or 1.0 mg/kg, once weekly for 4 weeks (Groups 3 and 4), or twice weekly for 4 weeks (Groups 5 and 6). Upon necropsy, left lungs were paraffin embedded, serially sectioned, and stained for histopathological examination. A subset was evaluated by immunohistochemistry (IHC), anti-pan cytokeratin staining AE1/AE3+ tumor cells and CD11b+ staining dendritic cells, natural killer lymphocytes, and macrophage immune cells (n = 2, Group 1; n = 3 each for Groups 2–6). BCL-6 staining identified B lymphocytes (n = 1 in Groups 1, 2, and 6). Results: All animals survived to scheduled necropsy, exhibited no adverse clinical observations due to treatment, and gained weight at the same rate throughout the study. Histopathological evaluation of Group 1 lung samples was consistent with unabated tumor growth. Group 2 exhibited regression in 10% of animals (n = 2/20). IH NanoPac-treated groups exhibited significantly higher tumor regression incidence per group (n = 11–13/20; p < 0.05, χ2). IHC subset analysis revealed tumor-nodule cluster separation, irregular borders between tumor and non-neoplastic tissue, and an increased density of infiltrating CD11b+ cells in Group 2 animals (n = 2/3) and in all IH NanoPac-treated animals reviewed (n = 3/3 per group). A single animal in Group 4 and Group 6 exhibited signs of pathological complete response at necropsy with organizing stroma and immune cells replacing areas presumed to have previously contained adenocarcinoma nodules. Conclusion: Tumor regression and immune cell infiltration were observed in all treatment groups, with an increased incidence noted in animals receiving IH submicron particle paclitaxel treatment.
Collapse
Affiliation(s)
- James Verco
- US Biotest, Inc., San Luis Obispo, California
| | | | - Michael Frost
- Western Diagnostic Services Laboratory, Santa Maria, California
| | | | | | - Anita Lopez
- Lovelace Biomedical, Albuquerque, New Mexico
| | | | | | | | - Gere diZerega
- US Biotest, Inc., San Luis Obispo, California.,NanOlogy, LLC, Fort Worth, Texas
| |
Collapse
|
|
16
|
Zivanovic O, Chi DS, Filippova O, Randall LM, Bristow RE, O'Cearbhaill RE. It's time to warm up to hyperthermic intraperitoneal chemotherapy for patients with ovarian cancer. Gynecol Oncol 2018; 151:555-561. [PMID: 30249527 PMCID: PMC6684262 DOI: 10.1016/j.ygyno.2018.09.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Revised: 09/01/2018] [Accepted: 09/06/2018] [Indexed: 01/05/2023]
Abstract
The peritoneal spread of ovarian cancer makes it a potential target for hyperthermic intraperitoneal chemotherapy (HIPEC). Intraperitoneal delivery exposes the tumor to concentrations of cytotoxic drugs much greater than with intravenous delivery, and in vitro studies have also shown that combining hyperthermia and platinum leads to an additive cytotoxic effect. Pharmacokinetic analyses have confirmed very high concentrations of cytotoxic drugs in the peritoneal cavity, with minimal systemic exposure and toxicity. The majority of historical data evaluating HIPEC in ovarian cancer are based on retrospective research, which included heterogeneous groups of patients and drugs used for HIPEC. Recent publications on the findings of prospective studies, including the first randomized trial in which the only difference in intervention was the addition of HIPEC with cisplatin to interval debulking surgery in stage III patients, have shown a benefit in favor of HIPEC. Yet, a recent prospective study from Korea did not find a benefit. Opponents of HIPEC have cited higher rates of complications with this approach, yet most of the serious adverse events observed are likely related to the surgery itself, and are comparable to the rates reported in studies evaluating cytoreductive surgery without HIPEC. Findings from a recent randomized controlled trial showed no delays in initiation or completion of postoperative chemotherapy in patients treated with HIPEC. A growing body of evidence is indicating that it might be time to seriously consider HIPEC as a complementary treatment at the time of cytoreductive surgery for patients with advanced-stage ovarian cancer in the setting of an experienced center. Yet, more research is needed to identify the population of patients who gain the most benefit from this therapy.
Collapse
Affiliation(s)
- Oliver Zivanovic
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA.
| | - Dennis S Chi
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA
| | - Olga Filippova
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Leslie M Randall
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Irvine Medical Center, University of California, Orange, CA, USA
| | - Robert E Bristow
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Irvine Medical Center, University of California, Orange, CA, USA
| | - Roisin E O'Cearbhaill
- Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA
| |
Collapse
|
|
17
|
Hyperthermic Intraperitoneal Perfusion Chemotherapy and Cytoreductive Surgery for Controlling Malignant Ascites From Ovarian Cancer. Int J Gynecol Cancer 2018; 26:1571-1579. [PMID: 27779544 DOI: 10.1097/igc.0000000000000809] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Malignant ascites, a complication often seen in patients with ovarian cancer (OC), is difficult to treat, but hyperthermic intraperitoneal chemotherapy (HIPEC) has a good efficacy. OBJECTIVE The aim of this study was to assess the efficacy of cytoreductive surgery (CRS) combined with HIPEC for controlling malignant ascites from OC. MATERIALS AND METHODS From December 2009 until December 2014, 53 patients with OC and malignant ascites were treated with CRS and HIPEC. Patients in good health condition were treated with CRS followed by HIPEC (CRS + HIPEC), and patients in poor health condition were treated initially with B-mode ultrasound-guided HIPEC followed by delayed CRS upon improvement of their health condition (HIPEC + delayed CRS). Resolution of ascites, complete CRS, overall survival, and disease-free survival were analyzed. RESULTS All patients showed ascites regression. The total objective remission rate was 100%, even for patients in the poor condition group before CRS. Complete CRS was successful in 30 (88.23%) of 34 patients in the good condition group, and 17 (89.47%) of 19 patients in the poor condition group (P > 0.05). Median disease-free survival and median overall survival were 21 and 39 months in the good condition group, and 22 and 38 months in the poor condition group, respectively (P > 0.05). CONCLUSIONS Hyperthermic intraperitoneal chemotherapy is effective at controlling ascites in patients with OC, even for patients in poor condition before CRS, or when complete CRS is not feasible. Furthermore, the regression of ascites appears not to be dependent on complete resection.
Collapse
|
|
18
|
Nowacki M, Peterson M, Kloskowski T, McCabe E, Guiral DC, Polom K, Pietkun K, Zegarska B, Pokrywczynska M, Drewa T, Roviello F, Medina EA, Habib SL, Zegarski W. Nanoparticle as a novel tool in hyperthermic intraperitoneal and pressurized intraperitoneal aerosol chemotheprapy to treat patients with peritoneal carcinomatosis. Oncotarget 2017; 8:78208-78224. [PMID: 29100461 PMCID: PMC5652850 DOI: 10.18632/oncotarget.20596] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Accepted: 08/15/2017] [Indexed: 12/11/2022] Open
Abstract
The treatment of peritoneal surface malignances has changed considerably over the last thirty years. Unfortunately, the palliative is the only current treatment for peritoneal carcinomatosis (PC). Two primary intraperitoneal chemotherapeutic methods are used. The first is combination of cytoreductive surgery (CRS) and Hyperthermic IntraPEritoneal Chemotherapy (HIPEC), which has become the gold standard for many cases of PC. The second is Pressurized IntraPeritoneal Aerosol Chemotheprapy (PIPAC), which is promising direction to minimally invasive as safedrug delivery. These methods were improved through multicenter studies and clinical trials that yield important insights and solutions. Major method development has been made through nanomedicine, specifically nanoparticles. Here, we are presenting the latest advances of nanoparticles and their application to precision diagnostics and improved treatment strategies for PC. These advances will likely develop both HIPEC and PIPAC methods that used for in vitro and in vivo studies. Several benefits of using nanoparticles will be discussed including: 1) Nanoparticles as drug delivery systems; 2) Nanoparticles and Near Infrred (NIR) Irradiation; 3) use of nanoparticles in perioperative diagnostic and individualized treatment planning; 4) use of nanoparticles as anticancer dressing's, hydrogels and as active beeds for optimal reccurence prevention; and 5) finally the curent in vitro and in vivo studies and clinical trials of nanoparticles. The current review highlighted use of nanoparticles as novel tools in improving drug delivery to be effective for treatment patients with peritoneal carcinomatosis.
Collapse
Affiliation(s)
- Maciej Nowacki
- Chair of Department of Surgical Oncology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Oncology Centre of Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Poland
| | - Margarita Peterson
- Department of Plastic and Reconstructive Surgery, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Tomasz Kloskowski
- Chair of Urology, Department of Regenerative Medicine, Ludwik Rydygier's Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Toruń, Poland
| | - Eleanor McCabe
- Department of Plastic and Reconstructive Surgery, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Delia Cortes Guiral
- Department of General Surgery (Peritoneal Surface Surgical Oncology), Fundación Jiménez Díaz Hospital, Madrid, Spain
| | - Karol Polom
- General Surgery and Surgical Oncology Department, University of Siena, Siena, Italy
- Department of Surgical Oncology, Medical University of Gdansk, Gdansk, Poland
| | - Katarzyna Pietkun
- Chair of Cosmetology and Aesthetic Dermatology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun. Bydgoszcz, Poland
| | - Barbara Zegarska
- Chair of Cosmetology and Aesthetic Dermatology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun. Bydgoszcz, Poland
| | - Marta Pokrywczynska
- Chair of Urology, Department of Regenerative Medicine, Ludwik Rydygier's Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Toruń, Poland
| | - Tomasz Drewa
- Chair of Urology, Department of Regenerative Medicine, Ludwik Rydygier's Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Toruń, Poland
| | - Franco Roviello
- Chair of Cosmetology and Aesthetic Dermatology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun. Bydgoszcz, Poland
| | - Edward A. Medina
- Department of Pathology, University of Texas Health, San Antonio, TX, USA
| | - Samy L. Habib
- Department of Cell Systems and Anatomy, University of Texas Health Geriatric Research Education, San Antonio, TX, USA
- South Texas Veterans Health Care System, San Antonio, TX, USA
| | - Wojciech Zegarski
- Chair of Department of Surgical Oncology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Oncology Centre of Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Poland
| |
Collapse
|
|
19
|
Arjona-Sanchez A, Rufián-Peña S. Progress in the management of primary and recurrent ovarian carcinomatosis with peritonectomy procedure and HIPEC in a high volume centre. Int J Hyperthermia 2017; 33:554-561. [DOI: 10.1080/02656736.2017.1278631] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Affiliation(s)
- Alvaro Arjona-Sanchez
- Unit of Oncologic and Pancreatic Surgery, University Hospital Reina Sofia, Cordoba, Spain
- CIBERehd, IMIBIC, University Hospital Reina Sofia, Cordoba, Spain
| | - Sebastian Rufián-Peña
- Unit of Oncologic and Pancreatic Surgery, University Hospital Reina Sofia, Cordoba, Spain
- CIBERehd, IMIBIC, University Hospital Reina Sofia, Cordoba, Spain
| |
Collapse
|
|
20
|
de Bree E, Michelakis D, Stamatiou D, Romanos J, Zoras O. Pharmacological principles of intraperitoneal and bidirectional chemotherapy. Pleura Peritoneum 2017; 2:47-62. [PMID: 30911633 PMCID: PMC6405033 DOI: 10.1515/pp-2017-0010] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Accepted: 04/05/2017] [Indexed: 12/19/2022] Open
Abstract
Intraperitoneal chemotherapy is associated with a significant pharmacokinetic and pharmacodynamic benefit and can, alone or in combination with systemic chemotherapy (bidirectional chemotherapy), be used for treating primary and secondary peritoneal surface malignancies. Due to the peritoneal-plasma barrier, high intraperitoneal drug concentration can be achieved by intraperitoneal chemotherapy, whereas systemic concentration remains low. Bidirectional chemotherapy may provide in addition adequate drug concentrations from the side of the subperitoneal space to the peritoneal tumour nodules. Major pharmacological problems of intraperitoneal chemotherapy are limited tissue penetration and poor homogeneity of drug distribution to the entire seroperitoneal surface. Significant pharmacological determinants of intraperitoneal chemotherapy are choice of drug, drug dosage, solution volume, carrier solution, intra-abdominal pressure, temperature, duration, mode of administration, extent of peritonectomy and interindividual variability. Drugs most commonly applied for intraperitoneal chemotherapy include mitomycin C, cisplatin, carboplatin, oxaliplatin, irinotecan, 5-fluoruracil, gemcitabine, paclitaxel, docetaxel, doxorubicin, premetrexed and melphalan. The drugs and their doses that are used vary widely among centres. While the adequate drug choice for intraperitoneal and bidirectional chemotherapy is essential, randomized clinical trials to determine the most optimal drug or drug combination are lacking, and only eight retrospective comparative clinical studies are available. Further clinical pharmacological studies are required to determine the most effective drug regimen for intraperitoneal and bidirectional chemotherapy in various indications. In the future, reliable drug sensitivity testing and genetic profiling of peritoneal metastases will be needed for enabling patient-specific therapy.
Collapse
Affiliation(s)
- Eelco de Bree
- Department of Surgical Oncology, Medical School of Crete University Hospital, Heraklion, Greece
| | - Dimosthenis Michelakis
- Department of Surgical Oncology, Medical School of Crete University Hospital, Heraklion, Greece
| | - Dimitris Stamatiou
- Department of Surgical Oncology, Medical School of Crete University Hospital, Heraklion, Greece
| | - John Romanos
- Department of Surgical Oncology, Medical School of Crete University Hospital, Heraklion, Greece
| | - Odysseas Zoras
- Department of Surgical Oncology, Medical School of Crete University Hospital, Heraklion, Greece
| |
Collapse
|
|
21
|
Coccolini F, Acocella F, Morosi L, Brizzola S, Ghiringhelli M, Ceresoli M, Davoli E, Ansaloni L, D'Incalci M, Zucchetti M. High Penetration of Paclitaxel in Abdominal Wall of Rabbits after Hyperthermic Intraperitoneal Administration of Nab-Paclitaxel Compared to Standard Paclitaxel Formulation. Pharm Res 2017; 34:1180-1186. [PMID: 28247168 DOI: 10.1007/s11095-017-2132-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 02/20/2017] [Indexed: 01/30/2023]
Abstract
PURPOSE Paclitaxel (PTX) is currently used in combination with cisplatin for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis. Albumin-bound PTX is a promising new drug for HIPEC because of its easy solubility in aqueous perfusion medium and possibly because of the tendency of albumin to cross physiological barriers and accumulate in tumor tissue. METHODS We tested the feasibility of using nab-paclitaxel in rabbits treated by HIPEC for 60 min compared with the classical formulation at an equivalent PTX dose. Samples of perfusate and blood were collected at different time points and peritoneal tissues were collected at the end of perfusion. PTX concentrations were determined by HPLC. The depth of paclitaxel penetration through the peritoneal barrier was assessed by mass spectrometry imaging. RESULTS PTX after nab-paclitaxel treatment penetrated up to 0.63 mm in the peritoneal wall, but after CRE-paclitaxel, it was not detectable in the peritoneum. Moreover, the peritoneal concentration after nab-paclitaxel was five times that after paclitaxel classical formulation. Despite the high levels reached in the peritoneum, systemic exposure of PTX was low. CONCLUSIONS Our results show that nab-paclitaxel penetrates into the abdominal wall better than CRE-paclitaxel, in terms of effective penetration and peritoneal tissue concentration.
Collapse
Affiliation(s)
- Federico Coccolini
- General, Emergency and Trauma Surgery Department Papa Giovanni XXIII hospital, Bergamo, Italy
| | - Fabio Acocella
- Dipartimento di Scienze Veterinarie per la Salute, la Produzione Animale e la Sicurezza Alimentare, Università degli Studi di Milano, Milan, Italy
| | - Lavinia Morosi
- Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
| | - Stefano Brizzola
- Dipartimento di Scienze Veterinarie per la Salute, la Produzione Animale e la Sicurezza Alimentare, Università degli Studi di Milano, Milan, Italy
| | - Matteo Ghiringhelli
- Dipartimento di Scienze Veterinarie per la Salute, la Produzione Animale e la Sicurezza Alimentare, Università degli Studi di Milano, Milan, Italy
| | - Marco Ceresoli
- General, Emergency and Trauma Surgery Department Papa Giovanni XXIII hospital, Bergamo, Italy
| | - Enrico Davoli
- Mass Spectrometry Laboratory, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
| | - Luca Ansaloni
- General, Emergency and Trauma Surgery Department Papa Giovanni XXIII hospital, Bergamo, Italy
| | - Maurizio D'Incalci
- Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
| | - Massimo Zucchetti
- Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
| |
Collapse
|
|
22
|
Spiliotis J, Halkia E, de Bree E. Treatment of peritoneal surface malignancies with hyperthermic intraperitoneal chemotherapy-current perspectives. ACTA ACUST UNITED AC 2016; 23:e266-75. [PMID: 27330364 DOI: 10.3747/co.23.2831] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Peritoneal carcinomatosis (ptc) represents advanced malignant disease and has generally been associated with a grim prognosis. Peritoneal surface malignancy is often the major source of morbidity and mortality; it is of major concern in cancer management. Although ptc is categorized as metastatic disease, it represents a special disease pattern considered to be a locoregional disease limited to the abdominal cavity. The combination of cytoreductive surgery (crs) and intraoperative hyperthermic intraperitoneal chemotherapy (hipec) has successfully been used as locoregional treatment for selected patients with ptc from gastric, colorectal, and ovarian cancer; with mesothelioma; and with pseudomyxoma peritonei. In the prophylactic setting, hipec can also be used to prevent ptc in high-risk patients, and the first results of the "second-look" approach are promising. Patient selection-in which the risks of perioperative morbidity and mortality, which are analogous to those for any other major gastrointestinal surgery, are assessed-is of utmost importance. Those risks have to be weighed against the anticipated survival benefit, which depends mainly on tumour biology, extent of disease, and probability of achieving complete crs. The present review discusses the principles of crs and hipec, the most significant recent clinical data, and current perspectives concerning the application of this treatment modality in various malignancies. Ongoing trials and future directions are noted. It appears that the combination of crs and hipec is an indispensable tool in the oncologist's armamentarium.
Collapse
Affiliation(s)
- J Spiliotis
- 1st Department of Surgery, Metaxa Cancer Institute, Piraeus, Greece
| | - E Halkia
- Peritoneal Surface Malignancy Unit, iaso General Hospital, Athens, Greece
| | - E de Bree
- Department of Surgical Oncology, Medical School of Crete University Hospital, Heraklion, Greece
| |
Collapse
|
|
23
|
Sánchez-García S, Villarejo-Campos P, Padilla-Valverde D, Amo-Salas M, Martín-Fernández J. Intraperitoneal chemotherapy hyperthermia (HIPEC) for peritoneal carcinomatosis of ovarian cancer origin by fluid and CO2 recirculation using the closed abdomen technique (PRS-1.0 Combat): A clinical pilot study. Int J Hyperthermia 2016; 32:488-95. [PMID: 27056558 DOI: 10.3109/02656736.2016.1152515] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Background This paper reports a study of 21 patients with peritoneal carcinomatosis from ovarian cancer who underwent cytoreductive surgery and HIPEC by means of PRS-1.0 Combat®, a new model for closed abdomen HIPEC aimed at improving fluid distribution with assistance from a CO2 recirculation system. This new technology has been previously shown to be successful in an experimental study (pig model) performed by our group, and has been approved for use in our hospital. Methods Twenty-one patients with peritoneal carcinomatosis of ovarian cancer origin were included in the study. Cytoreductive surgery and HIPEC were performed by a closed abdomen fluid and CO2 recirculation technique using the PRS-1.0 Combat(®) model. We analysed the intraoperative safety tolerance and post-operative morbidity and mortality during the first 30 days. Results Between November 2011 and March 2014 21 patients with epithelial ovarian cancer, International Federation of Gynecology and Obstetrics stage II-IV, were included in the study. During the procedure there were no significant haemodynamic or analytical disturbances. Complication rates were 38.1% and 57.14% for grade III/IV and minor (grade I/II) complications, respectively. Post-operative mortality was 4.76% (one patient). Complete cytoreductive surgery and intraperitoneal chemotherapy improved overall survival and disease-free survival in women with advanced ovarian cancer. The association of intra-abdominal hyperthermia with chemotherapy (HIPEC) increased the therapeutic benefit. Conclusions This study has shown that closed abdomen intraperitoneal chemohyperthermia by a fluid and CO2 recirculation system (PRS-1.0 Combat(®)) can be a safe and feasible model for the treatment of peritoneal carcinomatosis of ovarian cancer origin.
Collapse
Affiliation(s)
| | | | | | - Mariano Amo-Salas
- c Deparment of Mathematics , University of Castilla la Mancha , Spain
| | | |
Collapse
|
|
24
|
Boisen MM, Richard SD, Holtzman MP, Edwards RP, Kelley JL, Choudry MH, Bartlett D, Huang M. Hyperthermic intraperitoneal chemotherapy for epithelial ovarian cancers: is there a role? J Gastrointest Oncol 2016; 7:10-7. [PMID: 26941980 DOI: 10.3978/j.issn.2078-6891.2015.103] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Hyperthermic intraperitoneal chemotherapy (HIPEC) is often used to treat gastrointestinal malignancies and is of interest in epithelial ovarian cancer (EOC) given the propensity for intraperitoneal spread. The role of HIPEC in the treatment of gynecologic malignancies is not well defined. We sought to describe clinical characteristics and outcomes of our patient population treated with HIPEC. METHODS IRB approval was obtained. Patients diagnosed with EOC and treated with HIPEC from January 2007 until December 2013 were identified using a prospectively maintained HIPEC database. Patient charts were abstracted to identify patient demographic information, treatment characteristics, and outcome data. Statistical analysis was descriptive. RESULTS Thirty-four patients were identified. Mean age at diagnosis was 56.5 years. The majority of cases (28, 82%) were of serous histology. The indications for HIPEC administration were as follows: 9% primary treatment, 41% first recurrence, 26% second recurrence, and 24% consolidative therapy in the setting of primary or recurrent disease. The majority of patients (21, 62%) received mitomycin C. The other drugs administered include cisplatin (10, 29%), oxaliplatin (2, 6%), and carboplatin (1, 3%). Mean length of hospital stay was 9 days (range, 3-39 days). The rates of postoperative bacteremia and hematologic toxicity were 6% and 54%, respectively. Seven (21%) patients developed transient renal dysfunction, and this was seen almost exclusively in the patients who received cisplatin. One (3%) additional patient had renal dysfunction that persisted longer than 30 days post-operative but did not go on to require dialysis. There were no perioperative deaths in this cohort. Eleven (32%) patients received additional chemotherapy following HIPEC administration. At a median follow-up of 20 months (range, 3-87 months), eight patients are alive with disease, seven have no evidence of disease, 14 have died of their disease, and five patients have been lost to follow-up. CONCLUSIONS This data supports a reasonable side effect profile of treatment of EOC with HIPEC. Prospective studies are needed to elucidate the optimal drug and patient population that would derive the most benefit from treatment with HIPEC.
Collapse
Affiliation(s)
- Michelle M Boisen
- 1 Division of Gynecologic Oncology, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA ; 2 Division of Gynecologic Oncology, Hahnemann University Hospital, Philadelphia, PA, USA ; 3 Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Scott D Richard
- 1 Division of Gynecologic Oncology, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA ; 2 Division of Gynecologic Oncology, Hahnemann University Hospital, Philadelphia, PA, USA ; 3 Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Matthew P Holtzman
- 1 Division of Gynecologic Oncology, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA ; 2 Division of Gynecologic Oncology, Hahnemann University Hospital, Philadelphia, PA, USA ; 3 Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Robert P Edwards
- 1 Division of Gynecologic Oncology, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA ; 2 Division of Gynecologic Oncology, Hahnemann University Hospital, Philadelphia, PA, USA ; 3 Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Joseph L Kelley
- 1 Division of Gynecologic Oncology, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA ; 2 Division of Gynecologic Oncology, Hahnemann University Hospital, Philadelphia, PA, USA ; 3 Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Mohammad Haroon Choudry
- 1 Division of Gynecologic Oncology, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA ; 2 Division of Gynecologic Oncology, Hahnemann University Hospital, Philadelphia, PA, USA ; 3 Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - David Bartlett
- 1 Division of Gynecologic Oncology, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA ; 2 Division of Gynecologic Oncology, Hahnemann University Hospital, Philadelphia, PA, USA ; 3 Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Marilyn Huang
- 1 Division of Gynecologic Oncology, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA ; 2 Division of Gynecologic Oncology, Hahnemann University Hospital, Philadelphia, PA, USA ; 3 Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| |
Collapse
|
|
25
|
Muñoz-Casares F, Medina-Fernández F, Arjona-Sánchez Á, Casado-Adam Á, Sánchez-Hidalgo J, Rubio M, Ortega-Salas R, Muñoz-Villanueva M, Rufián-Peña S, Briceño F. Peritonectomy procedures and HIPEC in the treatment of peritoneal carcinomatosis from ovarian cancer: Long-term outcomes and perspectives from a high-volume center. Eur J Surg Oncol 2016; 42:224-33. [DOI: 10.1016/j.ejso.2015.11.006] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2015] [Revised: 10/27/2015] [Accepted: 11/09/2015] [Indexed: 12/11/2022] Open
|
|
26
|
Cascales-Campos P, Gil J, Feliciangeli E, Parrilla P. HIPEC in ovarian cancer: Treatment of a new era or is it the end of the pipeline? Gynecol Oncol 2015; 139:363-8. [DOI: 10.1016/j.ygyno.2015.06.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2015] [Revised: 05/15/2015] [Accepted: 06/08/2015] [Indexed: 01/21/2023]
|
|
27
|
Helm CW. Hyperthermic intraperitoneal chemotherapy for ovarian cancer: is there a role? J Gynecol Oncol 2015; 26:1-2. [PMID: 25609161 PMCID: PMC4302278 DOI: 10.3802/jgo.2015.26.1.1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
|
|
28
|
A phase I study of intraperitoneal nanoparticulate paclitaxel (Nanotax®) in patients with peritoneal malignancies. Cancer Chemother Pharmacol 2015; 75:1075-87. [PMID: 25898813 DOI: 10.1007/s00280-015-2737-4] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2014] [Accepted: 03/24/2015] [Indexed: 10/23/2022]
Abstract
PURPOSE This multicenter, open-label, dose-escalating, phase I study evaluated the safety, tolerability, pharmacokinetics and preliminary tumor response of a nanoparticulate formulation of paclitaxel (Nanotax®) administered intraperitoneally for multiple treatment cycles in patients with solid tumors predominantly confined to the peritoneal cavity for whom no other curative systemic therapy treatment options were available. METHODS Twenty-one patients with peritoneal malignancies received Nanotax® in a modified dose-escalation approach utilizing an accelerated titration method. All patients enrolled had previously received chemotherapeutics and undergone surgical procedures, including 33 % with optimal debulking. Six doses (50-275 mg/m(2)) of Cremophor-free Nanotax® were administered intraperitoneally for one to six cycles (every 28 days). RESULTS Intraperitoneal (IP) administration of Nanotax® did not lead to increases in toxicity over that typically associated with intravenous (IV) paclitaxel. No patient reported ≥Grade 2 neutropenia and/or ≥Grade 3 neurologic toxicities. Grade 3 thrombocytopenia unlikely related to study medication occurred in one patient. The peritoneal concentration-time profile of paclitaxel rose during the 2 days after dosing to peritoneal fluid concentrations 450-2900 times greater than peak plasma drug concentrations and remained elevated through the entire dose cycle. Best response assessments were made in 16/21 patients: Four patients were assessed as stable or had no response and twelve patients had increasing disease. Five of 21 patients with advanced cancers survived longer than 400 days after initiation of Nanotax® IP treatment. CONCLUSIONS Compared to IV paclitaxel administration, Cremophor-free IP administration of Nanotax® provides higher and prolonged peritoneal paclitaxel levels with minimal systemic exposure and reduced toxicity.
Collapse
|
|
29
|
Braam HJ, Schellens JH, Boot H, van Sandick JW, Knibbe CA, Boerma D, van Ramshorst B. Selection of chemotherapy for hyperthermic intraperitoneal use in gastric cancer. Crit Rev Oncol Hematol 2015; 95:282-96. [PMID: 25921419 DOI: 10.1016/j.critrevonc.2015.04.004] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Revised: 01/22/2015] [Accepted: 04/07/2015] [Indexed: 12/21/2022] Open
Abstract
PURPOSE Several studies have shown the potential benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients. At present the most effective chemotherapeutic regime in HIPEC for gastric cancer is unknown. The aim of this review was to provide a comprehensive overview of chemotherapeutic agents used for HIPEC in gastric cancer. METHODS A literature search was conducted using the PubMed database to identify studies on chemotherapy used for HIPEC in gastric cancer patients. RESULTS AND CONCLUSION The chemotherapeutic regime of choice in HIPEC for gastric cancer has yet to be determined. The wide variety in studies and study parameters, such as chemotherapeutic agents, dosage, patient characteristics, temperature of perfusate, duration of perfusion, carrier solutions, intraperitoneal pressure and open or closed perfusion techniques, warrant more experimental and clinical studies to determine the optimal treatment schedule. A combination of drugs probably results in a more effective treatment.
Collapse
Affiliation(s)
- H J Braam
- Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands.
| | - J H Schellens
- Division of Clinical Pharmacology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Science Faculty, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
| | - H Boot
- Division of Gastroenterology and Hepatology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - J W van Sandick
- Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - C A Knibbe
- Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - D Boerma
- Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - B van Ramshorst
- Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands
| |
Collapse
|
|
30
|
Li J, Tang J, Li Y, Yu J, Zhang B, Yu C. Pharmacokinetic profile of paclitaxel in the plasma, lung, and diaphragm following intravenous or intrapleural administration in rats. Thorac Cancer 2015; 6:43-8. [PMID: 26273334 PMCID: PMC4448465 DOI: 10.1111/1759-7714.12139] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2014] [Accepted: 05/12/2014] [Indexed: 12/04/2022] Open
Abstract
Background The optimal chemotherapy route for non-small cell lung cancers involving the phrenic nerve and diaphragm is unclear. The pharmacokinetic properties of paclitaxel following intravenous (IV) or intrapleural (IP) administration were analyzed in the plasma, lung, and diaphragm in a rat model. The purpose of this study was to determine whether IP injection increased paclitaxel concentration in the diaphragm. Methods Paclitaxel was administered by IV or IP to male Sprague-Dawley rats. The concentration of drug in the plasma, lung, and diaphragm was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters area under the curve (AUC), mean residence time (MRT), peak plasma concentration (Cmax), and half-life (t1/2) were analyzed. Results Paclitaxel concentration in the plasma, lung, and diaphragm decreased quickly following IV administration. However, after IP injection, paclitaxel reached a high concentration in the plasma, lung, and diaphragm that declined gradually. Significant differences in all parameters, except Cmax in the lung, were observed between the two routes of administration (all P < 0.05). Plasma exposure to paclitaxel IP was 41.1% of that observed after IV in the first 24 hours (P < 0.05). IP also significantly increased exposure of paclitaxel in comparison with IV administration to 267.3% and 905.7% of IV administration in the lung and diaphragm, respectively (P < 0.05). Conclusion These results suggest that IP administration may reduce systemic distribution of paclitaxel and increase the concentration in the lung and diaphragm. This could increase therapeutic efficacy by increasing the available drug and reduce systemic toxicity.
Collapse
Affiliation(s)
- Jie Li
- Department of Chest Surgery, The General Hospital of The People's Liberation Army Beijing, China ; Department of Cardio-thoracic Surgery, First Affiliated Hospital, General Hospital of PLA Beijing, China
| | - Jian Tang
- Department of Cardio-thoracic Surgery, First Affiliated Hospital, General Hospital of PLA Beijing, China
| | - Yingjie Li
- Department of Cardio-thoracic Surgery, First Affiliated Hospital, General Hospital of PLA Beijing, China
| | - Jianqi Yu
- Department of Cardio-thoracic Surgery, First Affiliated Hospital, General Hospital of PLA Beijing, China
| | - Baoshi Zhang
- Department of Cardio-thoracic Surgery, First Affiliated Hospital, General Hospital of PLA Beijing, China
| | - Changhai Yu
- Department of Cardio-thoracic Surgery, First Affiliated Hospital, General Hospital of PLA Beijing, China
| |
Collapse
|
|
31
|
Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer. Br J Cancer 2014; 112:306-12. [PMID: 25461804 PMCID: PMC4453456 DOI: 10.1038/bjc.2014.602] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2014] [Revised: 10/24/2014] [Accepted: 11/01/2014] [Indexed: 12/20/2022] Open
Abstract
Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) is advised as a treatment option for epithelial ovarian cancer (EOC) with peritoneal carcinomatosis. This study was designed to define the pharmacokinetics of cisplatin (CDDP) and paclitaxel (PTX) administered together during HIPEC. Methods: Thirteen women with EOC underwent cytoreductive surgery (CRS) and HIPEC, with CDDP and PTX. Blood, peritoneal perfusate and tissue samples were harvested to determine drug exposure by high-performance liquid chromatography and matrix-assisted laser desorption ionization imaging mass spectrometry (IMS). Results: The mean maximum concentrations of CDDP and PTX in perfusate were, respectively, 24.8±10.4 μg ml−1 and 69.8±14.3 μg ml−1; in plasma were 1.87±0.4 μg ml−1 and 0.055±0.009 μg ml−1. The mean concentrations of CDDP and PTX in peritoneum at the end of HIPEC were 23.3±8.0 μg g−1 and 30.1±18.3 μg−1g−1, respectively. The penetration of PTX into the peritoneal wall, determined by IMS, was about 0.5 mm. Grade 3–4 surgical complications were recorded in four patients, five patients presented grade 3 and two patients presented grade 4 hematological complications. Conclusions: HIPEC with CDDP and PTX after CRS is feasible with acceptable morbidity and has a favorable pharmacokinetic profile: high drug concentrations are achieved in peritoneal tissue with low systemic exposure. Larger studies are needed to demonstrate its efficacy in patients with microscopic postsurgical residual tumours in the peritoneal cavity.
Collapse
|
|
32
|
Yonemura Y, Canbay E, Endou Y, Ishibashi H, Mizumoto A, Miura M, Li Y, Liu Y, Takeshita K, Ichinose M, Takao N, Hirano M, Sako S, Tsukiyama G. Peritoneal cancer treatment. Expert Opin Pharmacother 2014; 15:623-36. [PMID: 24617975 DOI: 10.1517/14656566.2014.879571] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION In the past, peritoneal surface malignancy (PSM) was considered as a final stage of cancer, and patients were offered the best supportive care. Recently, a new therapeutic alternative approach based on the combination of surgery with chemotherapy was developed. In this curative intent, the macroscopic disease was treated with cytoreductive surgery (CRS) combined with perioperative chemotherapy, including neoadjuvant chemotherapy, hyperthermic intraoperative intraperitoneal chemotherapy, extensive intraoperative peritoneal lavage and early postoperative intraperitoneal chemotherapy AREAS COVERED This article reviews the mechanisms of the formation of PSM, quantitative estimation of PSM and residual disease, multimodal treatment, value of laparoscopy, prognostic factors and patients' selection for the multimodal therapy. EXPERT OPINION Recent studies show that CRS plus intraperitoneal chemotherapy applications confer prolonged survival in patients with PSM from colorectal, gastric, ovarian, appendiceal mucinous carcinoma and diffuse malignant peritoneal mesothelioma. The comprehensive treatment is now justified as state-of-the-art for patients with peritoneal metastasis.
Collapse
Affiliation(s)
- Yutaka Yonemura
- NPO Organization to Support Peritoneal Surface Malignancy Treatment , Oosaka , Japan
| | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
33
|
Population pharmacokinetics of peritoneal, plasma ultrafiltrated and protein-bound oxaliplatin concentrations in patients with disseminated peritoneal cancer after intraperitoneal hyperthermic chemoperfusion of oxaliplatin following cytoreductive surgery: correlation between oxaliplatin exposure and thrombocytopenia. Cancer Chemother Pharmacol 2014; 74:571-82. [PMID: 25053386 DOI: 10.1007/s00280-014-2525-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2014] [Accepted: 07/06/2014] [Indexed: 12/17/2022]
Abstract
PURPOSE First, to evaluate the peritoneal (IP), plasma ultrafiltrated (UF) and protein-bound (B) pharmacokinetics (PK) of oxaliplatin after intraperitoneal hyperthermic chemoperfusion (HIPEC) following cytoreductive surgery. Second, to evaluate the relationship between oxaliplatin exposure and observed toxicity. METHODS IP, UF, and B concentrations from 75 patients treated by 30-min oxaliplatin-based HIPEC procedures were analysed according to a pharmacokinetic modelling approach using NONMEM. Oxaliplatin was administered in a 5 % dextrose solution (2 L/m(2)) at 360 (n = 58) or 460 mg/m(2) (n = 17). The most frequently observed toxicities were related to the peritoneal, systemic exposures and to the parameters corresponding to the oxaliplatin absorption from peritoneal cavity into plasma. RESULTS IP (n = 536), UF (n = 669) and B (n = 661) concentrations were simultaneously described according to a five-compartment PK model with irreversible nonlinear binding from UF to B according to a Michaelis-Menten equation. The mean (±SD) maximum fraction of dose absorbed and elimination half-life from the peritoneum was 53.7 % (±8.5) and 0.49 h (±0.1), respectively. The mean (±SD) ratio AUC(IP)/AUC(UF) was 5.3 (±2) confirming the pharmacokinetic advantage of the procedure. Haemoperitoneum (22.7 %), neuropathy (18.7 %), grade 3/4 thrombocytopenia (13.3 %) were the most frequently reported toxicities. AUC(UF) accounts for approximately 12 % of the variation in the maximum percentage of platelet decrease (r = 0.35, p = 0.002). Thrombocytopenia was correlated with higher AUCUF, partly dependent on the extent and rate of oxaliplatin absorption. CONCLUSIONS Despite a common dose administered, variability in peritoneal and systemic oxaliplatin exposures are observed, leading to differences in haematological toxicity between patients.
Collapse
|
|
34
|
LC–MS/MS quantitative analysis of paclitaxel and its major metabolites in serum, plasma and tissue from women with ovarian cancer after intraperitoneal chemotherapy. J Pharm Biomed Anal 2014; 91:131-7. [DOI: 10.1016/j.jpba.2013.12.028] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Revised: 12/17/2013] [Accepted: 12/21/2013] [Indexed: 11/20/2022]
|
|
35
|
Security and efficiency of a closed-system, turbulent-flow circuit for hyperthermic intraperitoneal chemotherapy after cytoreductive ovarian surgery: perioperative outputs. Arch Gynecol Obstet 2014; 290:121-9. [PMID: 24488579 DOI: 10.1007/s00404-014-3153-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2013] [Accepted: 01/09/2014] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To present physiologic intraoperative data and immediate postoperative outcomes of patients diagnosed with epithelial ovarian cancer submitted to cytoreductive surgery and hyperthermic peritoneal intraoperative chemotherapy (HIPEC) with a closed-circuit, turbulent-flow system. MATERIALS AND METHODS A closed-circuit system with CO2 turbulent flow was used for paclitaxel HIPEC during 60 min for patients diagnosed with stage II or higher and recurrent epithelial ovarian cancer. Perioperative hemodynamic and metabolic statuses were followed, as well as physiologic recovery during the first 12 postoperative hours. A non-parametric statistical analysis was performed. RESULTS At the end of the hyperthermia phase, temperature was 37.7 ± 0.6 °C, heart rate 88 ± 19 bpm, cardiac index 2.8 ± 0.5 L min(-1) m(-2), stroke volume variation 14.6 ± 3.6 % and extravascular lung water 8.7 ± 1.9 mL kg(-1). No hyperdynamic status was recorded. The length of stay in the ICU was 2½ days, and 12.7 ± 7 days in hospital. Average postoperative intubation time was 11.7 ± 17.4 h. At the ICU admission time, glucose, lactic acid and hemoglobin were the only values out of range, but close to normal. SOFA median was 3 at admission and 0 the following day. CONCLUSION A turbulent-flow, closed-circuit use for hyperthermic peritoneal intraoperative chemotherapy resulted in no hyperdynamic response or coagulopathy, had good tolerance and promoted early physiologic recovery.
Collapse
|
|
36
|
Lotti M, Busci LM, Campanati L, Catena F, Coccolini F, Bakrin N, Iaco PD, Ercolani G, Grosso G, Pisano M, Poiasina E, Rossetti D, Rossi M, Zamagni C, Bertoli P, Pinna AD, Frigerio L, Ansaloni L. Cytoreductive surgery and HIPEC after neoadjuvant chemotherapy for advanced epithelial ovarian cancer. World J Obstet Gynecol 2013; 2:167-175. [DOI: 10.5317/wjog.v2.i4.167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2013] [Revised: 04/23/2013] [Accepted: 07/11/2013] [Indexed: 02/05/2023] Open
Abstract
AIM: To reduce postoperative complications and to make possible an optimal cytoreduction, neoadjuvant chemotherapy (NACT) followed by interval debulking surgery has been applied with encouraging results.
METHODS: Between December 2009 and February 2012, patients with stage IIIC-IV epithelial ovarian cancer (EOC) underwent diagnostic laparoscopy, to assess the feasibility of optimal debulking surgery. The modified Fagotti score was applied to assess the feasibility of resection with zero residual tumor. Patients who were not candidate for upfront debulking surgery were submitted to NACT, then reassessed according to the RECIST 1.1 criteria and submitted to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) if they showed clinical response or stable disease. The remaining cycles of adjuvant systemic chemotherapy (ASCT) were administered postoperatively, to complete 6 cycles of systemic chemotherapy.
RESULTS: Nine patients were included. Clinical response to NACT was complete in 3 patients and partial in 5 patients; one patient had stable disease. All patients underwent CRS resulting in CC0 disease prior to HIPEC. Average operative time was 510 min. Average intensive care unit stay was 2 d. Average postoperative hospital stay was 25 d. No postoperative mortality was observed. One patient experienced pelvic abscess. One patient refused ASCT. The remaining 8 patients started ASCT. Average time to chemotherapy was 36 d. All patients are alive, with an average follow up of 11 mo. Eight patients are disease-free at follow up.
CONCLUSION: HIPEC after CRS for advanced EOC is feasible with acceptable morbidity and mortality. NACT may increase the chance for achieving complete cytoreduction. Phase 3 studies are needed to determine the effects of HIPEC on survival.
Collapse
|
|
37
|
de Bree E, Helm CW. Hyperthermic intraperitoneal chemotherapy in ovarian cancer: rationale and clinical data. Expert Rev Anticancer Ther 2013; 12:895-911. [PMID: 22845405 DOI: 10.1586/era.12.72] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The outcome of ovarian cancer remains poor with conventional therapy. Intraperitoneal chemotherapy has some advantages over systemic chemotherapy, including favorable pharmacokinetics and optimal treatment timing. Intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) provides improved exposure of the entire seroperitoneal surface to the agent and utilizes the direct cytoxic and drug-enhancing effect of hyperthermia. While standard normothermic, nonintraoperative, intraperitoneal chemotherapy has been demonstrated to be beneficial in randomized trials and meta-analyses, there are no data from randomized HIPEC trials available yet. Cautious extrapolation of data from standard normothermic, nonintraoperative, intraperitoneal chemotherapy and data from Phase II and nonrandomized comparative studies suggest that HIPEC delivered at the time of surgery for ovarian cancer has definite potential. Data from ongoing randomized HIPEC trials to adequately answer the question of whether the addition of HIPEC actually prolongs survival in patients with peritoneal dissemination of primary and recurrent ovarian cancer are awaited in the near future.
Collapse
Affiliation(s)
- Eelco de Bree
- Department of Surgical Oncology, Medical School of Crete-University Hospital, PO Box 1352, 71110 Heraklion, Greece.
| | | |
Collapse
|
|
38
|
Coccolini F, Catena F, Manfredi R, Lotti M, Frigerio L, Ansaloni L. Advanced ovarian cancer: Neoadjuvant chemotherapy plus surgery and HIPEC as up-front treatment. World J Obstet Gynecol 2012; 1:55-59. [DOI: 10.5317/wjog.v1.i4.55] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Epithelial ovarian cancer (EOC) is one of the most common malignancies and one of the principal causes of death in gynecological neoplasms. The majority of EOC patients present with an advanced International Federation of Gynecology and Obstetrics stage disease. The current standard treatment for these patients consists of complete cytoreduction and combined systemic chemotherapy of a platinum agent and paclitaxel. Even if the majority of patients with EOC respond to first-line platinum based chemotherapy, almost 20% of them are resistant or refractory. According to these data, the main risk is for a certain number of patients to have undergone cytoreductive surgery (CRS) and subsequent hyperthermic intraoperative peritoneal chemotherapy (HIPEC) in a useful way. Radical surgery, especially in advanced cases, is associated with a high incidence of postoperative morbidity and mortality, which could be increased by the HIPEC. Every effort should be made for previously selected patients to improve outcome and optimize resources. Over the last decade, new options have been introduced to prolong survival. Improved long-term results can be achieved using CRS in combination with intraoperative HIPEC. This combination has also been used in an up-front setting. Controversial outcomes have been reported for neoadjuvant platinum-based chemotherapy. Different papers have been published reporting discordant results. Further studies are needed.
Collapse
|
|
39
|
Pharmacokinetics of the perioperative use of cancer chemotherapy in peritoneal surface malignancy patients. Gastroenterol Res Pract 2012; 2012:378064. [PMID: 22778722 PMCID: PMC3384921 DOI: 10.1155/2012/378064] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2012] [Accepted: 04/23/2012] [Indexed: 01/25/2023] Open
Abstract
Background. The peritoneal surface is an acknowledged locoregional failure site of abdominal malignancies. Previous treatment attempts with medical therapy alone did not result in long-term survival. During the last two decades, new treatment protocols combining cytoreductive surgery with perioperative intraperitoneal and intravenous cancer chemotherapy have demonstrated very encouraging clinical results. This paper aims to clarify the pharmacologic base underlying these treatment regimens. Materials and Methods. A review of the current pharmacologic data regarding these perioperative chemotherapy protocols was undertaken. Conclusions. There is a clear pharmacokinetic and pharmacodynamic rationale for perioperative intraperitoneal and intravenous cancer chemotherapy in peritoneal surface malignancy patients.
Collapse
|
|
40
|
Development of a Nanocrystalline Paclitaxel Formulation for Hipec Treatment. Pharm Res 2012; 29:2398-406. [DOI: 10.1007/s11095-012-0765-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2012] [Accepted: 04/20/2012] [Indexed: 10/28/2022]
|
|
41
|
Imano M, Imamoto H, Itoh T, Satou T, Peng YF, Yasuda A, Kato H, Shiraishi O, Shinkai M, Yasuda T, Takeyama Y, Okuno K, Shiozaki H. Safety of intraperitoneal administration of paclitaxel after gastrectomy with en-bloc D2 lymph node dissection. J Surg Oncol 2011; 105:43-7. [PMID: 21837682 DOI: 10.1002/jso.22065] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2011] [Accepted: 07/20/2011] [Indexed: 01/26/2023]
Abstract
BACKGROUND The aim of this study was to examine the safety, pharmacokinetics, and cytological efficacy against free intraperitoneal cancer cells of intraperitoneal chemotherapy (IPC) with paclitaxel after gastrectomy with en-bloc D2 lymph node dissection (GD2) in cases of gastric cancer with peritoneal carcinomatosis (PC) and/or positive cytological findings in peritoneal washings (CFPW). METHODS Twenty-one patients with gastric cancer with PC and/or positive CFPW who underwent GD2 were treated with early, post-operative, intraperitoneal paclitaxel. Intra-chemotherapeutic toxicity and operative complication were measured using the common toxicity criteria of the National Cancer Institute, version 3.0. Intraperitoneal and plasma paclitaxel concentrations were measured using a high-performance liquid chromatography assay. RESULTS Grade 3 anemia occurred in two patients (9.5%) and neutropenia was observed in three patients (14.3%). No grade 4 toxicity was observed. A grade 2 operative complication was a superficial surgical site infection (4.8%) that was treated with antibiotics. Cytologically, no viable cancer cells were observed in the intra-abdominal fluid 24 hr after intraperitoneal administration of paclitaxel. The intraperitoneal/plasma area under the drug concentration-time curve (AUC) ratio was 596.9:1. CONCLUSION IPC with paclitaxel after GD2 is a safe and cytologically effective treatment modality for free intraperitoneal cancer cells. However, additional data are required to determine the effect on survival.
Collapse
Affiliation(s)
- Motohiro Imano
- Department of Surgery, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
42
|
Cyto-reductive Surgery combined with Hyperthermic Intra-peritoneal Chemotherapy for Peritoneal Surface Malignancies: current treatment and results. Cancer Treat Rev 2011; 38:258-68. [PMID: 21807464 DOI: 10.1016/j.ctrv.2011.07.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2011] [Revised: 07/03/2011] [Accepted: 07/06/2011] [Indexed: 02/06/2023]
Abstract
Cyto-reductive Surgery (CS) combined with Hyperthermic Intra-peritoneal Chemotherapy (HIPEC) as loco-regional treatment of Peritoneal Surface Malignancies (PSM) has increasingly gained acceptance in clinical practice. This review summarizes the more relevant studies on this topic. Indications, pre-operative work-up, technical aspects, outcome and future directions of this combined approach in the treatment of Peritoneal Surface Malignancies are discussed here and proposed in an informative and didactic manner.
Collapse
|
|
43
|
Antitumour efficacy of two paclitaxel formulations for hyperthermic intraperitoneal chemotherapy (HIPEC) in an in vivo rat model. Pharm Res 2011; 28:1653-60. [PMID: 21424162 DOI: 10.1007/s11095-011-0401-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2010] [Accepted: 02/14/2011] [Indexed: 12/14/2022]
Abstract
PURPOSE To evaluate the tumour growth delay of a peritoneal carcinomatosis (PC) of colorectal origin after intraperitoneal chemotherapy with paclitaxel/randomly-methylated-β-cyclodextrin (Pac/RAME-β-CD) versus Taxol® at normo- and hyperthermic conditions in rats. METHODS Hyperthermic intraperitoneal chemotherapy (HIPEC) was performed 7 days post implantation of the tumour with both formulations at a Pac concentration of 0.24 mg/ml. Tumour evaluation was performed via positron emission tomography (PET) and magnetic resonance imaging (MRI) imaging, measuring tumour activity and tumour volume, respectively. Scans were taken at 2 and 7 days post treatment. RESULTS PET and MRI data showed a significant reduction in tumour activity and tumour volume for rats treated with Pac/RAME-β-CD (at normo- and hyperthermic conditions), compared to the control group. Treatment with Taxol® did not result in a significant reduction of tumour activity and tumour volume. No significant differences between the normo- and hyperthermic conditions were observed for both formulations, indicating that hyperthermia and paclitaxel were not synergistic despite the direct cytotoxic effect of hyperthermia. CONCLUSION Monitoring tumour growth via PET and MRI indicated that Pac/RAME-β-CD inclusion complexes had a significantly higher efficacy compared to Taxol® in a rat model for peritoneal carcinomatosis.
Collapse
|
|
44
|
Valenzuela B, Nalda-Molina R, Bretcha-Boix P, Escudero-Ortíz V, Duart MJ, Carbonell V, Sureda M, Rebollo JP, Farré J, Brugarolas A, Pérez-Ruixo JJ. Pharmacokinetic and pharmacodynamic analysis of hyperthermic intraperitoneal oxaliplatin-induced neutropenia in subjects with peritoneal carcinomatosis. AAPS JOURNAL 2011; 13:72-82. [PMID: 21210260 DOI: 10.1208/s12248-010-9249-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/04/2010] [Accepted: 12/14/2010] [Indexed: 12/18/2022]
Abstract
The objective of this study was to characterize the pharmacokinetics and the time course of the neutropenia-induced by hyperthermic intraperitoneal oxaliplatin (HIO) after cytoreductive surgery in cancer patients with peritoneal carcinomatosis. Data from 30 patients who received 360 mg/m(2) of HIO following cytoreductive surgery were used for pharmacokinetic-pharmacodynamic (PK/PD) analysis. The oxaliplatin plasma concentrations were characterized by an open two-compartment pharmacokinetic model after first-order absorption from peritoneum to plasma. An oxaliplatin-sensitive progenitor cell compartment was used to describe the absolute neutrophil counts in blood. The reduction of the proliferation rate of the progenitor cells was modeled by a linear function of the oxaliplatin plasma concentrations. The typical values of oxaliplatin absorption and terminal half-lives were estimated to be 2.2 and 40 h, with moderate interindividual variability. Oxaliplatin reduced the proliferation rate of the progenitor cells by 18.2% per mg/L. No patient's covariates were related to oxaliplatin PK/PD parameters. Bootstrap and visual predictive check evidenced the model was deemed appropriate to describe oxaliplatin pharmacokinetics and the incidence and severity of neutropenia. A peritoneum oxaliplatin exposure of 65 and 120 mg·L/h was associated with a 20% and 33% incidence of neutropenia grade 4. The time course of neutropenia following HIO administration was well described by the semiphysiological PK/PD model. The maximum tolerated peritoneum oxaliplatin exposure is 120 mg L/h and higher exposures should be avoided in future studies. We suggest the prophylactic use of granulocyte colony stimulating factor for patients treated with HIO exposure higher than 65 mg L/h.
Collapse
Affiliation(s)
- Belén Valenzuela
- Platform of Oncology, USP Hospital San Jaime, Partida de Loma s/n, 03184 Torrevieja, Alicante, Spain.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
45
|
Advanced cytoreduction as surgical standard of care and hyperthermic intraperitoneal chemotherapy as promising treatment in epithelial ovarian cancer. Eur J Surg Oncol 2010; 37:4-9. [PMID: 21112721 DOI: 10.1016/j.ejso.2010.11.004] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2010] [Revised: 10/26/2010] [Accepted: 11/01/2010] [Indexed: 12/12/2022] Open
Abstract
Favorable oncological outcomes have been reported in several trials with the introduction of Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the treatment of Advanced Epithelial Ovarian Cancer (EOC). However most of the studies testing the combined approach are observational and have been conducted in inhomogeneous series so that the evidence supporting the performance of this combined treatment is still poor. Median Overall and Disease Free Survivals of up to 64 months and 57 months, respectively have been reported. Although a rate of morbidity of up to 40% has been observed in some series the CRS + HIPEC continues to gain an increased popularity. Several prospective randomized trials are ongoing using the procedure in various time points of the disease. In this review several issues such as the impact of cytoreduction and residual disease (RD) on outcomes as well as the role of HIPEC will be updated from the literature evidence. Some controversial points HIPEC related will also be discussed. Recent experiences regarding the introduction of a more aggressive surgical approach to upper abdomen to resect peritoneal carcinomatosis (PC) allowed increased rates of optimal cytoreduction and has demonstrated an apparent better outcome. This evidence associated with the positive results phase III trial testing normothermic intraperitoneal as first-line chemotherapy is guiding some investigators to propose the CRS + HIPEC in the primary setting. Several prospective phase II and III trials have recently been launched to validate the role of the combined treatment in various time points of disease natural evolution.
Collapse
|
|
46
|
Sharma A, Meena AS, Bhat MK. Hyperthermia-associated carboplatin resistance: differential role of p53, HSF1 and Hsp70 in hepatoma cells. Cancer Sci 2010; 101:1186-93. [PMID: 20180806 PMCID: PMC11159963 DOI: 10.1111/j.1349-7006.2010.01516.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Due to substantial technical improvements, clinical application of heat as a co-adjuvant in cancer treatment is acquiring new interest. The effect of hyperthermia on hepatoma cell lines Hep3B (p53 defective) and HepG2 (p53 wild type) when investigated led to an interesting observation that Hep3B cells are more susceptible to heat stress than HepG2 cells. In addition, heat-induced carboplatin resistance was observed in HepG2 cells only. To investigate the reasons, heat shock response was explored and it was observed that heat stress augmented heat shock protein 70 (Hsp70) expression levels in HepG2 and not in Hep3B cells. Furthermore, in HepG2 cells, induced Hsp70 is regulated by both p53 and heat shock transcription factor 1 (HSF1) wherein HSF1 levels are modulated by p53. The data implies that Hep3B are more susceptible to death upon heat stress than HepG2 cells because of non-induction of Hsp70. In addition, it was observed that inhibition of heat-induced p53/HSF1 diminishes Hsp70 levels, thereby restoring the sensitivity of heat-stressed HepG2 cells to carboplatin-triggered cell death. Collectively, the present study establishes interplay of p53, HSF1, and Hsp70 upon heat stress in HepG2 cells and also defines novel strategies to overcome constraints of utility of hyperthermia in cancer therapy through p53/HSF1-targeted therapeutic intervention.
Collapse
|
|
47
|
Bouquet W, Ceelen W, Adriaens E, Almeida A, Quinten T, De Vos F, Pattyn P, Peeters M, Remon JP, Vervaet C. In vivo toxicity and bioavailability of Taxol and a paclitaxel/beta-cyclodextrin formulation in a rat model during HIPEC. Ann Surg Oncol 2010; 17:2510-7. [PMID: 20339948 DOI: 10.1245/s10434-010-1028-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2009] [Indexed: 01/19/2023]
Abstract
BACKGROUND Peritoneal carcinomatosis (PC) remains a dreaded clinical syndrome and a common evolution of gastrointestinal and ovarian cancers. In recent years, hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery has emerged as a promising strategy in the management of PC. In this study, a novel paclitaxel (Pac) formulation was investigated for its toxicity and bioavailability during HIPEC compared with Taxol. MATERIALS AND METHODS The maximum tolerated dose (MTD) after HIPEC of both formulations (Taxol and Pac/RAME-beta-CD) was determined. MTD was defined as the highest nonlethal dose with a reduction in body weight of < or = 10% over 2 weeks. Blood parameters (red blood cell and white blood cell count, creatinine, ALT, and GGT) were evaluated over 20 days. Bioavailability of both Pac formulations after HIPEC was determined under normothermic (37 degrees C) and hyperthermic (41 degrees C) conditions for 90 min. RESULTS Following HIPEC, both formulations had a similar MTD: 0.24 mg paclitaxel per ml. Red blood cell count decreased to a minimum after 10 days and was not fully recovered after 20 days for both formulations. White blood cell monitoring showed a significant increase in neutrocytes at day 10 and 15 for the Pac/RAME-beta-CD formulation. Liver and kidney parameters did not change significantly. Bioavailability data of Pac/RAME-beta-CD showed a 40-fold increase of the area under the curve (AUC) of plasma concentrations compared with Taxol. Hyperthermia yielded no significant differences in bioavailability data. CONCLUSION These results showed that both formulations had a similar toxicity profile but differed significantly in bioavailability.
Collapse
Affiliation(s)
- W Bouquet
- Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
48
|
Fagotti A, Gallotta V, Romano F, Fanfani F, Rossitto C, Vizzielli G, Costantini B, Scambia G. Role of cytoreductive surgery in recurrent ovarian cancer. ACTA ACUST UNITED AC 2010. [DOI: 10.2217/thy.09.90] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
|
|
49
|
Kim JH, Lee JM, Ryu KS, Lee YS, Park YG, Hur SY, Lee KH, Lee SH, Kim SJ. Consolidation hyperthermic intraperitoneal chemotherapy using paclitaxel in patients with epithelial ovarian cancer. J Surg Oncol 2009; 101:149-55. [DOI: 10.1002/jso.21448] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
|
|
50
|
Muñoz-Casares FC, Rufián S, Rubio MJ, Díaz CJ, Díaz R, Casado Á, Arjona Á, Muñoz-Villanueva MC, Muntané J. The role of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinomatosis in recurrent ovarian cancer. Clin Transl Oncol 2009; 11:753-9. [DOI: 10.1007/s12094-009-0438-3] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
|