A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study |
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Authors: | Gould Natalie Sill Michael W Mannel Robert S Thaker P H Disilvestro Paul Waggoner Steve Yamada S Diane Armstrong Deborah K Wenzel Lari Huang Helen Fracasso Paula M Walker Joan L |
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Institution: | a Division of Gynecologic Oncology, Women's Cancer Center of Nevada, Las Vegas NV 89169, USAb Gynecologic Oncology Group Statistical and Data Center, Buffalo NY 14263, USAc Division of Gynecologic Oncology, University of Oklahoma, OK 73190, USAd Division of Gynecologic Oncology, Washington University, St Louis, MO 63110, USAe Division of Gynecologic Oncology, Women and Infants Hospital, Providence RI 02905, USAf Division of Gynecologic Oncology, Case Western Reserve University, Cleveland, OH 44106, USAg Section of Gynecologic Oncology, University of Chicago, Chicago IL 60637, USAh Gynecology and Obstretrics, Johns Hopkins Oncology Center, Baltimore, MD 21231, USAi Center for Health Policy Research, University of California, Irvine, Irvine, CA 92697, USAj Department of Medicine and the UVA Cancer Center, University of Virginia, Charlottesville VA 22908, USA |
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Abstract: | ObjectiveTo define the maximum tolerated dose (MTD) and assess the feasibility of intravenous (IV) paclitaxel, intraperitoneal (IP) carboplatin, and IP paclitaxel in women with newly diagnosed Stages II-IV ovarian, fallopian tube, or primary peritoneal carcinoma.MethodsPatients received escalating doses of paclitaxel IV and carboplatin IP on day 1 and paclitaxel IP 60 mg/m2 on day 8. A standard 3 + 3 design was used in the escalation phase. A two-stage group sequential design with 20 patients at the MTD was used in the feasibility phase. Patient-reported neurotoxicity was assessed pre and post treatment.ResultsPatients were treated with paclitaxel 175 mg/m2 IV and carboplatin IP from AUC 5-7 on day 1 and paclitaxel 60 mg/m2 IP on day 8. The MTD was estimated at carboplatin AUC 6 IP and 25 patients enrolled at this dose level. Within the first 4 cycles, seven (35%) of twenty evaluable patients had dose-limiting toxicities (DLTs) including grade 4 thrombocytopenia (1), grade 3 neutropenic fever (3), > 2 week delay due to ANC recovery (1), grade 3 LFT (1), and grade 3 infection (1). De-escalation to paclitaxel 135 mg/m2 IV was given to improve the safety. After six evaluable patients completed 4 cycles without a DLT, bevacizumab was added and six evaluable patients completed 4 cycles with one DLT (grade 3 hyponatremia).ConclusionsPaclitaxel at 175 mg/m2 IV, carboplatin AUC 6 IP day 1 and paclitaxel 60 mg/m2 IP day 8 yield 18-56% patients with DLTs. The tolerability of the regimen in combination with bevacizumab was indicated in a small cohort. |
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Keywords: | Phase I trial Intraperitoneal chemotherapy Carboplatin Paclitaxel Ovarian cancer |
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