Gemcitabine and oxaliplatin followed by paclitaxel and carboplatin as first line therapy for patients with advanced epithelial ovarian cancer. A phase II trial of sequential doublets. (GO-FIRST)

Abstract

5034 Background: Gemcitabine and oxaliplatin are active in epithelial ovarian cancer with minimal overlapping toxicity, and in pre-clinical studies have shown synergy. The primary objective of this prospective phase II study is to evaluate the response rate (RR) and toxicity of gemcitabine and oxaliplatin (GO) administered sequentially with paclitaxel and carboplatin (PC). Secondary objectives were time to progression, quality of life outcomes and overall survival. Methods: Patients with histologically proven epithelial ovarain cancer, FIGO stage II-IV, measurable disease (RECIST), and PS 0–2 were eligible. Treatment consisted of gemcitabine 1250mg/m2 D1, D8 and oxaliplatin 135mg/m2 D8 q21days for 4 cycles followed by carboplatin AUC6 and paclitaxel 175mg/m2 D1 q21days for 4 cycles. Interval debulking was permitted after 4 cycles. Results: 20 patients are enrolled. Median age 62 yrs (range 39–78), FIGO III-IV (16/4). 12/20 pts were only able to have an initial biopsy and of these, 7 were subsequently debulked. 4 cycles of GO were given prior to the planned 4 cycles of PC. The RR to 4 cycles of GO was 80% (CR4/PR12). With subsequent debulking surgery and further chemotherapy (PC) the final RR was 85% (13 CR/4 PR). One pt died of a PE and one progressed on GO and died. At a median F/U of 21 mths 15 pts are still alive, 6 without progression. The median TTP was 15.2 mths. Grade 3/4 toxicities for GO: nausea and vomiting 4pts (20%), neutropenia 4pts (20%). PC: alopecia 14 (70%), neutropenia 2 (10%), thrombocytopenia 1 (5%). Peripheral neuropathy was the major toxicity. 4 pts developed G2 and a further 1pt G3 on GO. With sequential PC, 8 pts developed G2 and 5 pts G3 neuropathy requiring dose reduction in 3 pts and cessation of paclitaxel in 6 pts. Conclusions: GO is a new doublet with activity in ovarian cancer, but sequential PC should not be used given the cumulative neurotoxicity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly