C N Krasner1, C Castro2, R T Penson2, M Roche3, U A Matulonis4, M A Morgan5, C Drescher6, D K Armstrong7, J K Wolfe8, H Lee2, J G Supko2, M Seiden9, M J Birrer10, D S Dizon11. 1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States of America. Electronic address: Carolyn_krasner@dfci.harvard.edu. 2. Department of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, United States of America. 3. Blueprint Bio, Cambridge, MA, United States of America. Electronic address: mroche2@blueprintmedicines.com. 4. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States of America. 5. Division of Gynecologic Oncology, University of Pennsylvania, Philadelphia, PA, United States of America. Electronic address: Mark.Morgan@uphs.upenn.edu. 6. Translational Research Program, Division of Gynecologic Oncology, Fred Hutchinson Cancer Center, Seattle, WA, United States of America. Electronic address: cdresche@fredhutch.org. 7. Department of Medical Oncology, Johns Hopkins University Medical Center, Baltimore, MD, United States of America. Electronic address: armstde@jhmi.edu. 8. Community Health, Indianapolis, IN, United States of America. Electronic address: JWolf4@ecommunity.com. 9. US Oncology, United States of America. Electronic address: Michael.seiden@mckesson.com. 10. Department of Medical Oncology, University of Alabama, Birmingham, AL, United States of America. Electronic address: mbirrer@uab.edu. 11. Department of Medical Oncology, Rhode Island Hospital, United States of America. Electronic address: don.dizon@lifespan.org.
Abstract
BACKGROUND: Intraperitoneal (IP) chemotherapy can improve outcomes for women with optimally cytoreduced epithelial ovarian cancer but toxicities are a concern. We conducted 2 phase 2 trials of an IV/IP regimen using carboplatin and paclitaxel without (Trial A) and with bevacizumab (Trial B). METHODS: Both trials consisted of carboplatin AUC 6 day 1, and paclitaxel 60 mg/m2 on days 1,8, 15 of a 21-day cycle; in Trial B, patients received IV bevacizumab 15 mg/kg every cycle starting cycle 2. Chemotherapy was administered IV for cycle 1 and then IP for all subsequent cycles. Primary objectives included safety and tolerability, pathologic CR rate (Trial A), and the rate of completion of IP cycles of therapy (Trial B). Progression-free (PFS), overall survival (OS), and pharmacokinetic analysis were secondary endpoints. RESULTS: 81 patients were treated on both trials (n = 40 and 41 in trials A and B, respectively). Median age for trials A and B was 59 (range, 36-76) and 55 (range, 19-69) years, respectively. 68% and 85% of patients, respectively for A and B, completed at least 4 cycles of treatment in both trials. Treatment with bevacizumab resulted in higher rates of grade 3 fatigue (37 versus 33%) and grade 3-4 diarrhea (22 versus 8%). Median PFS was 23.5 (95%CI 16.2-35.3) and 25 (95%CI 16.4-42.7) months, respectively; median OS was 68 (95%CI 49.5-NR) and 79.7 (95%CI 59.0-79.7) months, respectively for Trial A and B. CONCLUSIONS: Weekly administered IP carboplatin and IP paclitaxel is tolerable and safe with similar activity with and without concommittant bevacizumab in these 2 trials.
BACKGROUND: Intraperitoneal (IP) chemotherapy can improve outcomes for women with optimally cytoreduced epithelial ovarian cancer but toxicities are a concern. We conducted 2 phase 2 trials of an IV/IP regimen using carboplatin and paclitaxel without (Trial A) and with bevacizumab (Trial B). METHODS: Both trials consisted of carboplatin AUC 6 day 1, and paclitaxel 60 mg/m2 on days 1,8, 15 of a 21-day cycle; in Trial B, patients received IV bevacizumab 15 mg/kg every cycle starting cycle 2. Chemotherapy was administered IV for cycle 1 and then IP for all subsequent cycles. Primary objectives included safety and tolerability, pathologic CR rate (Trial A), and the rate of completion of IP cycles of therapy (Trial B). Progression-free (PFS), overall survival (OS), and pharmacokinetic analysis were secondary endpoints. RESULTS: 81 patients were treated on both trials (n = 40 and 41 in trials A and B, respectively). Median age for trials A and B was 59 (range, 36-76) and 55 (range, 19-69) years, respectively. 68% and 85% of patients, respectively for A and B, completed at least 4 cycles of treatment in both trials. Treatment with bevacizumab resulted in higher rates of grade 3 fatigue (37 versus 33%) and grade 3-4 diarrhea (22 versus 8%). Median PFS was 23.5 (95%CI 16.2-35.3) and 25 (95%CI 16.4-42.7) months, respectively; median OS was 68 (95%CI 49.5-NR) and 79.7 (95%CI 59.0-79.7) months, respectively for Trial A and B. CONCLUSIONS: Weekly administered IP carboplatin and IP paclitaxel is tolerable and safe with similar activity with and without concommittant bevacizumab in these 2 trials.