S Gouy1, G Ferron2, O Glehen3, A Bayar4, F Marchal5, C Pomel6, F Quenet7, J M Bereder8, M C Le Deley9, P Morice10. 1. Department of Surgery, Gustave Roussy, Villejuif, France. Electronic address: sebastien.gouy@gustaveroussy.fr. 2. Department of Surgery, Institut Claudius Regaud, Toulouse, France. 3. Department of Surgery, Hôpital Lyon Sud, Bénite, France. 4. Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France. 5. Department of Surgery and CRAN, UMR 7039, Université de Lorraine, CNRS Institut de Cancérologie de Lorraine Vandoeuvre-les-Nancy, France. 6. Department of Surgery, Centre Jean Perrin, Clermont-Ferrand, France. 7. Department of Surgery, Centre Val d'Aurelle, Montpellier, France. 8. Department of Surgery, Centre Hospitalier l'Archet II, Nice, France. 9. Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France; University Paris Sud, Villejuif, France. 10. Department of Surgery, Gustave Roussy, Villejuif, France; University Paris Sud, Villejuif, France.
Abstract
PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) may improve the outcome of patients with initially unresectable ovarian cancer who are eligible for complete cytoreductive surgery (CCRS) after neoadjuvant chemotherapy. The main objective of this multicenter phase-I study was to identify the recommended dose of cisplatin for HIPEC at CCRS after neoadjuvant carboplatin and paclitaxel (CP). METHODS: Patients were treated with 6cycles of CP followed by CCRS and HIPEC using cisplatin heated for one hour at 42°C+/-1°C. Four cisplatin dose-levels were evaluated: 50, 60, 70, 80mg/m(2). Dose-limiting toxicities (DLTs) were defined as a grade≥IIIb adverse event (Dindo classification). The Continual Reassessment Method was used for this dose-finding study, with a target percentage of DLT set at 20%. Twenty-two cycles (15mg/kg/cycle) of maintenance bevacizumab therapy were planned after surgery. RESULTS: Between June-2011 and September-2012, 30 patients were recruited. No DLT occurred at the first three dose-levels (4, 4 and 5 patients at 50, 60 and 70mg/m(2) respectively). At dose-level 4 (80mg/m(2), 17 patients), four DLTs occurred: renal failure (n=2), peritonitis (n=1) and hemorrhage (n=1). Eight weeks after surgery, creatinine clearance was reduced to <30mL/min in 3 patients, all treated at 80mg/m(2), and between 30 and 60mL/min in 6 patients (2, 1, 1 and 2 at the four dose-levels respectively). Twenty patients started maintenance bevacizumab, and 7 received the 22 courses initially planned. CONCLUSIONS: Based on the observed DLTs and prolonged impairment of renal function, we recommend a dose of 70mg/m(2) of cisplatin for HIPEC.
PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) may improve the outcome of patients with initially unresectable ovarian cancer who are eligible for complete cytoreductive surgery (CCRS) after neoadjuvant chemotherapy. The main objective of this multicenter phase-I study was to identify the recommended dose of cisplatin for HIPEC at CCRS after neoadjuvant carboplatin and paclitaxel (CP). METHODS:Patients were treated with 6cycles of CP followed by CCRS and HIPEC using cisplatin heated for one hour at 42°C+/-1°C. Four cisplatin dose-levels were evaluated: 50, 60, 70, 80mg/m(2). Dose-limiting toxicities (DLTs) were defined as a grade≥IIIb adverse event (Dindo classification). The Continual Reassessment Method was used for this dose-finding study, with a target percentage of DLT set at 20%. Twenty-two cycles (15mg/kg/cycle) of maintenance bevacizumab therapy were planned after surgery. RESULTS: Between June-2011 and September-2012, 30 patients were recruited. No DLT occurred at the first three dose-levels (4, 4 and 5 patients at 50, 60 and 70mg/m(2) respectively). At dose-level 4 (80mg/m(2), 17 patients), four DLTs occurred: renal failure (n=2), peritonitis (n=1) and hemorrhage (n=1). Eight weeks after surgery, creatinine clearance was reduced to <30mL/min in 3 patients, all treated at 80mg/m(2), and between 30 and 60mL/min in 6 patients (2, 1, 1 and 2 at the four dose-levels respectively). Twenty patients started maintenance bevacizumab, and 7 received the 22 courses initially planned. CONCLUSIONS: Based on the observed DLTs and prolonged impairment of renal function, we recommend a dose of 70mg/m(2) of cisplatin for HIPEC.
Authors: Deepa Magge; Lekshmi Ramalingam; Yongli Shuai; Robert P Edwards; James F Pingpank; Steven S Ahrendt; Matthew P Holtzman; Herbert J Zeh; David L Bartlett; Haroon A Choudry Journal: J Surg Oncol Date: 2017-06-19 Impact factor: 3.454
Authors: Luigi Carlo Turco; Gabriella Ferrandina; Virginia Vargiu; Serena Cappuccio; Anna Fagotti; Giuseppina Sallustio; Giovanni Scambia; Francesco Cosentino Journal: Ann Transl Med Date: 2020-12