Phase II study of weekly topotecan in recurrent ovarian cancer: duration of response based on a prolonged follow-up

Abstract

16549 Background: Up to date the concept of “Stable Disease” (SD) as a clinical outcome is still considered a problematic endpoint. In a previous study we demonstrated that Topotecan, administered at a low weekly dosage (2,0 mg/m2) is an active option in the subset of heavily pretreated patients with recurrent platinum-resistant epithelial ovarian cancer (RprEOC) (Proc.ASCO, 2007; Abs. N°16076). In this phase II single arm trial, we explored the safety of the weekly topotecan with a particular interest in the duration of response, both in partial response and in stable disease. Methods: Nineteen patients (median age 52 yrs, range 45-72) with RprEOC who progressed after 3 (11/19 = 57.9%), 4 (7/19= 36.8%) or 5 (1/19= 5.3%) previous lines of chemotherapy were treated with Topotecan at the dose of 2.0 mg/m2 via a 30-minute i.v. infusion once every week until disease progression, unacceptable toxicity or when a stability of disease was reached. Results: All patients were evaluable for toxicity and clinical response. 16/19 pts enrolled (84.2%) had stage III-IV disease. Median number of chemotherapy cycles was 7 (range 3 - 12). A total of 107 cycles were administered. Dose reduction was necessary for 13% of the cycles. Main toxicities included anemia (grade I-II=57.9%), leucopenia (grade I-II=15.8%), thrombocytopenia (grade I-II=10.5%) and asthenia (20%). No one showed complete response, while 5/19 partial response (26.4%) and 6/19 stable disease (31.5%) were observed. 8/19 pts (42.1%) progressed on therapy. The median progression-free interval was 12 weeks in patients with partial response; stable disease was maintained for a median time of 14 weeks. Conclusion: Topotecan administered at low weekly dosage (2.0mg/m2) is an active option in the subset of heavily RprEOC and it seems also to be a very tolerable regimen compared to the classical 5-day schedule, characterized by an easy administration and absence of cumulative toxicities or cross-resistance In our experience the response obtained with this chemotherapeutic agent is of a particular interest because based on a prolonged follow-up. The rate of patients with ongoing stable disease (31.5%) suggests that the clinical benefit of weekly topotecan may be expected also in patients with no other viable therapeutic options. No significant financial relationships to disclose.