TOPOTECAN, AN ACTIVE-DRUG IN THE 2ND-LINE TREATMENT OF EPITHELIAL OVARIAN-CANCER - RESULTS OF A LARGE EUROPEAN PHASE-II STUDY

Purpose: Topotecan is a topoisomerase I inhibitor with preclinical act ivity against various tumor types. We conducted a large multicenter ph ase II study with topotecan in ovarian cancer in patients who held fai led to respond to one prior cisplatin-based chemotherapeutic regimen. Patients and Methods: Topotecan 1.5 mg/m(2)/d was administered intrave nously by 30-minute infusion for 5 days repeated every 3 weeks, As the cisplatin-free interval relates to response in subsequent treatment, patients were stratified in subgroups, ie, cisplatin-refractory, cispl atin-resistant, and cisplatin-sensitive. Results: One-hundred eleven p atients entered the study. Nineteen patients were considered to be ine ligible; 92 patients were assessable for response. A total of 552 cour ser were given (median, four per patient; range, one to 17). The major toxicities were leukocytopenia and neutropenia, which were grade 3 to 4 in 54.2% and 69.1% of courses, respectively, but with only 4.3% of these being grade 4 neutropenia plus fever or infectious complications . Prophylactic granulocyte colony-stimulating factor (G-CSF) was given in 20.5% of courses to maintain dose-intensity. Other relatively freq uent side effects were alopecia (82%), nausea (36.4%), and vomiting (1 7.5%). The overall response rate was 16.3%, with one complete response (CR) and 14 partial responses (PRs). In the cispla!tin-refractory, ci splatin-resistant, and cisplatin-sensitive strata, the response rates were 5.9% 17.8%, and 26.7%, respectively. The median duration of time of documented response was 21.7 weeks (range, 4.6 to 41.9). Conclusion : Topotecan in a daily-times-five schedule is an effective regimen as second-line treatment in ovarian cancer. Further investigations of top otecan in ovarian cancer, including first-line use and combination wit h other active agents, are indicated. (C) 1996 by American Society of Clinical Oncology.