Phase II study of the combination of pegylated liposomal doxorubicin and topotecan in platinum-resistant ovarian cancer.

The combination of liposomal doxorubicin and topotecan was evaluated in a phase II study in patients with platinum-resistant ovarian cancer. Twenty-seven patients received liposomal doxorubicin (30 mg/m(2)) infused at day 1, followed by topotecan (1 mg/m(2)) infusion daily for 5 days. Cycles were repeated every 21 days. This combination regimen showed an overall response rate of 28%. Median time to progression was 30 weeks, with a median overall survival of 40 weeks. Grade 3/4 neutropenia was shown in 70% of patients and grade 3/4 thrombopenia in 41% of patients. Neutropenic fever was reported in 11% of patients. After reviewing the first 12 patients, the internal review board decided to administer topotecan at a dose of 0.75 mg/m(2) and liposomal doxorubicin at 40 mg/m(2) for the remainder of the study. However, this adjustment did not lead to reduction in bone marrow toxicity nor to an improvement in dose intensity. Palmar-plantar erythrodysesthesia and mucositis were more reported in the second cohort but usually mild. The combination of liposomal doxorubicin and topotecan demonstrates favorable response data in platinum-resistant ovarian cancer. However, substantial bone marrow toxicity limits further clinical use.