Paclitaxel/Carboplatin (Tc) Vs. Paclitaxel/Carboplatin Followed By Topotecan (Top) In First-Line Treatment Of Advanced Ovarian Cancer. Mature Results Of A Gynecologic Cancer Intergroup Phase Iii Trial Of The Ago Ovar And Gineco.

LBA5007 Background: A randomized phase III trial was performed in patients (pts) with advanced ovarian cancer (OC) to determine the role of Top in first line treatment. The sequential manner was chosen to incorporate Top as a non cross resistant third drug to TC by avoiding the toxicity of a simultaneous triple drug regimen. Methods: Between 12/1999 and 03/2002 1,308 pts with previously untreated OC with FIGO stages IIb-IV were randomized to receive 6 cycles of Paclitaxel (175 mg/m2 3h iv) and Carboplatin (AUC 5, Calvert formula) (TC) followed by either no further therapy (n=650) or 4 cycles of Topotecan (1.25 mg/m2 iv d1–5) (Top) (n=658) on a 3 weekly schedule. The primary endpoint was overall survival (OS). This study was designed to show an increase in 3 year survival of 8% with a power of 0.8 using a log-rank test with alpha set to 0.05. Therefore 541 events are necessary. Results: Overall, 9417 treatment cycles were administered, 5535 in the TC-Top arm and 3882 in the TC arm. During treatment with TC, there was no significant difference in Grade (G) 3/4 hematologic and non-hematologic toxicity between both study arms. The median doses of TC were given as scheduled, as were the median intervals between therapy courses. 78% of pts who were randomized for Top received Top. The median number of Top courses was 4.0. Median Top dose/course/day for all courses was 1.25 mg/m2. Top myelotoxicity resulted in treatment delays of at least 7 days in 10.6% of courses. G 3/4 anemia occured in 6.4% of all Top courses, thrombocytopenia in 10.6% and neutropenia in 57.0%. However, this was of minimal clinical relevance in terms of febrile neutropenia (1.0%) or infections (0.9%). Response data were available from 141 and 143 pts with measurable disease in the TC and TC-Top arm. There was no statistically significant difference in CR and PR between treatment arms (76.2% for TC vs. 68.1% for TC-Top, p= n.s). Conclusions: The necessary events for OS are awaited within the next couple of weeks. The final efficacy analysis reporting on OS will be done in February 2005. Results will be submitted as late breaking abstract. No significant financial relationships to disclose.