A phase II study of topotecan plus gemcitabine in the treatment of patients with relapsed ovarian cancer after failure of first-line chemotherapy

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Abstract
Background: Second-line chemotherapy for patients with ovarian cancer who failed platinum and paclitaxel treatment remains a therapeutic challenge. We investigated the toxicity profile and therapeutic efficacy of a novel combination regimen, topotecan plus gemcitabine, in a clinical phase II study. Patients and methods: Women with relapsed epithelial ovarian cancer after platinum and paclitaxel treatment were eligible to participate in this trial. Topotecan was given at an initial dose of 0.5 mg/m2 daily (days 1–5), combined with gemcitabine 800 mg/m2 and 600 mg/m2 on days 1 and 8, respectively. Precluding good tolerability, this protocol facilitated subsequent dose increases of topotecan up to 1.0 mg/m2. The primary objective was to determine the dose-limiting toxicity, whereas secondary objectives comprised measurable and CA-125 response rates, disease-free and overall survival. Results: The twenty-one patients (median age 57 years, range 37–70 years) who were allocated to this trial received a total of 94 courses of chemotherapy. Median follow-up was 20.5 months. Topotecan dosage could be escalated to 0.75 mg/m2 in nine patients and 1 mg/m2 in another two patients. Dose reduction was not necessary in any case. There were no episodes of neutropenic fever, sepsis or chemotherapy-related fatalities. Only one patient developed CTC grade 4 leukopenia after the first treatment cycle, whereas three patients showed grade 3/4 anaemia. Five patients experienced thrombocytopenia grade 4 without clinical sequelae. Non-hematological toxicities were mild and rare. Eleven patients could be evaluated for clinical tumour response, with three complete, and four partial remissions. Two patients each had stable and progressive diseases. The median progression-free survival rate was 8.8 months [95% confidence interval (CI) 6.3–13.4 months]. The median overall survival rate was 21.1 months (95% CI 14.8–22.1 months). Conclusions: Topotecan combined with gemcitabine has a favourable toxicity profile and encouraging efficacy in patients with recurrent ovarian cancer.