BACKGROUND: The high incidence of dose-limiting myelosuppresion using the U.S. Food and Drug Administration-approved topotecan dose of 1.5 mg/m(2) for 5 days every 3 weeks may have limited its utility in the treatment of patients with epithelial ovarian carcinoma. The objective of the study was to evaluate the treatment results and toxicity of a low-dose topotecan regimen as second-line treatment for patients with epithelial ovarian carcinoma. METHODS: A retrospective analysis was conducted of 203 consecutive patients with primary epithelial ovarian carcinoma who were referred to the Finsen Center during the period from June, 1996 to June, 2000. Eligibility criteria included histopathologically documented, International Federation of Gynecology and Obstetrics (FIGO) Stage IC-IV epithelial ovarian carcinoma; first-line treatment with paclitaxel and a platinum compound; and second-line treatment with topotecan (1.0 mg/m(2) intravenously for 5 days every 3 weeks). Efficacy and toxicity were compared with published results from pivotal trials using the approved dose of topotecan of 1.5 mg/m(2) for the same indication. RESULTS: A total of 56 patients received second-line treatment with the reduced-dose topotecan regimen because of refractory, persistent, or recurrent disease. In the subgroup of patients with platinum-resistant and paclitaxel-resistant disease (n = 43 patients), the response rate of 11.6% (95% confidence interval [95%CI], 3.9-25.1%) was similar to the response rate of 12.4% (95%CI, 6.9-19.9%) in a pivotal trial using standard-dose topotecan. In patients with platinum-resistant and paclitaxel-resistant disease, the median progression free survival and overall survival from the first day of second-line topotecan treatment were 2.7 months (range, 0.7-19.5 months) and 6.0 months (range, 1.0-32.8 months), respectively. In a multivariate Cox analysis, the initial performance status (0 vs. 1-2; P = 0.040; hazard ratio [HR], 2.05) and the performance status at the time of second-line treatment (0 vs. 1-2; P < 0.001; HR, 4.50) were identified as independent prognostic factors for overall survival from the start of second-line treatment. Grade 4 neutropenia was noted in only 5.1% of reduced-dose topotecan cycles (95%CI, 2.8-8.4%) compared with 33% and 57% of standard-dose cycles in pivotal studies. CONCLUSIONS: Topotecan at a dose of 1.0 mg/m(2) has similar efficacy based on response rate and lower toxicity compared with the approved schedule of 1.5 mg/m(2) for 5 days every 3 weeks in second-line treatment for patients with platinum-resistant and paclitaxel-resistant epithelial ovarian carcinoma. However, a comparison of different topotecan doses and schedules preferably should be made in a randomized setting in well-characterized populations with regard to established prognostic factors. Copyright 2002 American Cancer Society.
BACKGROUND: The high incidence of dose-limiting myelosuppresion using the U.S. Food and Drug Administration-approved topotecan dose of 1.5 mg/m(2) for 5 days every 3 weeks may have limited its utility in the treatment of patients with epithelial ovarian carcinoma. The objective of the study was to evaluate the treatment results and toxicity of a low-dose topotecan regimen as second-line treatment for patients with epithelial ovarian carcinoma. METHODS: A retrospective analysis was conducted of 203 consecutive patients with primary epithelial ovarian carcinoma who were referred to the Finsen Center during the period from June, 1996 to June, 2000. Eligibility criteria included histopathologically documented, International Federation of Gynecology and Obstetrics (FIGO) Stage IC-IV epithelial ovarian carcinoma; first-line treatment with paclitaxel and a platinum compound; and second-line treatment with topotecan (1.0 mg/m(2) intravenously for 5 days every 3 weeks). Efficacy and toxicity were compared with published results from pivotal trials using the approved dose of topotecan of 1.5 mg/m(2) for the same indication. RESULTS: A total of 56 patients received second-line treatment with the reduced-dose topotecan regimen because of refractory, persistent, or recurrent disease. In the subgroup of patients with platinum-resistant and paclitaxel-resistant disease (n = 43 patients), the response rate of 11.6% (95% confidence interval [95%CI], 3.9-25.1%) was similar to the response rate of 12.4% (95%CI, 6.9-19.9%) in a pivotal trial using standard-dose topotecan. In patients with platinum-resistant and paclitaxel-resistant disease, the median progression free survival and overall survival from the first day of second-line topotecan treatment were 2.7 months (range, 0.7-19.5 months) and 6.0 months (range, 1.0-32.8 months), respectively. In a multivariate Cox analysis, the initial performance status (0 vs. 1-2; P = 0.040; hazard ratio [HR], 2.05) and the performance status at the time of second-line treatment (0 vs. 1-2; P < 0.001; HR, 4.50) were identified as independent prognostic factors for overall survival from the start of second-line treatment. Grade 4 neutropenia was noted in only 5.1% of reduced-dose topotecan cycles (95%CI, 2.8-8.4%) compared with 33% and 57% of standard-dose cycles in pivotal studies. CONCLUSIONS:Topotecan at a dose of 1.0 mg/m(2) has similar efficacy based on response rate and lower toxicity compared with the approved schedule of 1.5 mg/m(2) for 5 days every 3 weeks in second-line treatment for patients with platinum-resistant and paclitaxel-resistant epithelial ovarian carcinoma. However, a comparison of different topotecan doses and schedules preferably should be made in a randomized setting in well-characterized populations with regard to established prognostic factors. Copyright 2002 American Cancer Society.