3-day topotecan and carboplatin in first line treatment of optimally debulked ovarian cancer: A phase II trial

Abstract

5144 Background: Primary treatment of ovarian cancer has improved over the last 10 years, but overall 5-year survival is still poor. Initial in-vitro laboratory synergism studies have shown that the combination of carboplatin and topotecan is superior to the current standard of care.This study was undertaken to assess the toxicity and response of primary ovarian cancer to a combination of 3-day topotecan and 1-day carboplatin. Methods: Patients with primary stage III or IV optimally debulked, < 1 cm, ovarian or primary peritoneal cancer were treated with 3-day topotecan at 1 mg/m2 and carboplatin at AUC = 5, at 21 day intervals. Primary endpoint are objective response and toxicity with a planned accrual of 46 patients in 2 stages. Response will be defined by clinical exam, radiological exam and CA125 values. Results: Stage 1 accrual was completed in 2002 with a greater than 50% objective response and stage 2 was begun in 2004 due to a change in study site. Preliminary data shows 35 entered patients with 31 evaluable for response. The 35 patients have received a total of 185 courses of 3-day topotecan and carboplatin. All patients are evaluable for toxicity and 31 of 35 are evaluable for response with a median follow-up of 18 months. Twenty-eight of 31 patients have had a complete response for an overall response rate of 90.3%. Median time to recurrence has not been reached for the stage 1 patients. Hematologic toxicity is predominant with grade 3 or 4 neutropenia occurring in 66 of 185 courses (35%) but only 2 patients required delays. Colony stimulating factors were added for all patients having Grade 3 or 4 neutropenia or anemia. Grade 3 or 4 thrombocytopenia occurred in only 14 of 185 courses, with only 1 patient requiring platelet transfusion. Fatigue, alopecia and nausea were similar to other trials. Conclusions: These findings suggest that 3-day topotecan and carboplatin are well tolerated and are active in this early trial. Although the combination has some toxicity, it can be managed conservatively with supportive care and with few delays. Continued accrual and follow-up is planned on this trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline