Phase I/feasibility trial of dose-dense carboplatin (C) and paclitaxel (P) in patients (pts) with ovarian cancer: A Gynecologic Oncology Group study

Abstract

5544 Background: Dose-dense regimens improve outcome for women with breast cancer. We investigated the feasibility of dose-dense CP for women with ovarian cancer. Methods: Pts with untreated stage III/IV ovarian cancer received C AUC 5 and P 175 mg/m2 day 1, pegfilgrastim 6 mg day 2 every 2 weeks for 6 cycles. Dose-limiting toxicity (DLT) was defined as: febrile neutropenia, grade 4 neutropenia ≥7 days, grade 4 thrombocytopenia (tcp), grade 3 tcp with bleeding, dose delay >2 weeks, grade 3/4 non-hematologic toxicity (excluding fatigue, hypersensitivity, nausea/vomiting, alopecia, constipation, diarrhea or bone pain), and any treatment related death. The study utilized a 2-stage sequential design (20 pts/stage) with DLTs in 6 cycles determining regimen feasibility. Results: Between September 2006 and September 2008, 43 pts enrolled. Twenty and 17 patients were evaluable for toxicity over 6 cycles in stages 1 and 2 respectively. Six DLT's were observed for both stages. Thirty pts completed treatment and 12 did not [DLTs (6), paclitaxel hypersensitivity reactions (2), progression (1), patient choice (1), infection (1) and death unrelated to treatment (1)]. One pt remains on treatment. The 6 DLTs resulting in treatment discontinuation included grade 3 neuropathy (2), grade 4 neuropathy (1), grade 4 tcp (1), grade 4 tcp/grade 3 febrile neutropenia (1), and grade 4 SVT (1). Six other DLTs not preventing treatment completion included grade 3 infection (1), grade 3 AST/ALT elevation (1), grade 3 confusion (1), grade 3 dehydration (1), grade 3 neuropathy (1) and grade 4 tcp (1). Other toxicities resulting in treatment delays included grade 3 tcp (1), grade 3 fatigue (1) and grade 2 neuropathy (2). There were 5 P dose reductions and 4 C dose reductions. Conclusions: Seventy-two percent pts completed 6 cycles of dose-dense CP. Based on DLTs (at least 12 in 37 evaluable pts), this regimen is not feasible. Given the neuropathy and tcp, we do not recommend further investigation in a phase III trial. No significant financial relationships to disclose.