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Morgan MA , Darcy KM , Rose PG , DeGeest K , Bookman MA , Aikins JK , Sill MW , Mannel RS , Allievi C , Egorin MJ , Gynecologic Oncology Group
Paclitaxel poliglumex and carboplatin as first-line therapy in ovarian, peritoneal or fallopian tube cancer: a phase I and feasibility trial of the Gynecologic Oncology Group
Gynecol Oncol. 2008 Sep;110(3) :329-35
PMID: 18597837    PMCID: PMC2577579   
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PURPOSE: To estimate the maximum tolerated dose (MTD) of paclitaxel poliglumex (PPX) in combination with carboplatin in patients with chemotherapy-naive ovarian, primary peritoneal or fallopian tube cancer, and to assess the feasibility of administering multiple cycles of this regimen. METHODS: The first 11 patients were treated in a standard 3 + 3 dose-seeking design, with carboplatin held constant at area under the curve (AUC) of 6 and PPX at 225, 175 or 135 mg/m(2). Pharmacokinetics of PPX and carboplatin were evaluated during this dose-seeking component of the trial. MTD was defined by acute dose-limiting toxicities (DLT) in the first cycle. Twenty additional evaluable patients were treated at the estimated MTD to assess the feasibility of this regimen over >or=4cycles. RESULTS: PPX at 225 mg/m(2) resulted in DLT in 2/3 patients, and was de-escalated first to 175 mg/m(2) and then to 135 mg/m(2). PPX slowly hydrolyzed to paclitaxel and did not alter the pharmacokinetics of carboplatin. DLT within the first 4-cycles were observed in 3 patients (15%) treated at the MTD: neutropenia > 2weeks (2), febrile neutropenia (1). Nineteen patients (95%) experienced grade 4 neutropenia. Sixteen patients (80%) had at least one episode of grade 3 thrombocytopenia. Three patients (15%) had grade 2 and one had grade 3 peripheral neuropathy. Complete response by CA-125 was 75%. CONCLUSIONS: The recommended dose of PPX of 135 mg/m(2) with carboplatin (AUC = 6) in newly diagnosed ovarian cancer was feasible for multiple cycles, but hematologic toxicity was greater compared with standard carboplatin and 3-hour paclitaxel.
Morgan, Mark A Darcy, Kathleen M Rose, Peter G DeGeest, Koen Bookman, Michael A Aikins, James K Sill, Michael W Mannel, Robert S Allievi, Cecilia Egorin, Merrill J CA 27469/CA/NCI NIH HHS/United States CA 37517/CA/NCI NIH HHS/United States Clinical Trial, Phase I Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Gynecologic oncology Gynecol Oncol. 2008 Sep;110(3):329-35. Epub 2008 Jul 1.