Topotecan (Hycamtin®) in the Therapy of Small-Cell Lung Cancer

Abstract

Topotecan possesses a high antitumor activity in small-cell lung cancer (SCLC). Myelotoxicity was the dose-limiting factor, in particular neutropenia that developed in up to 80% of the patients, although it was of short duration and not cumulative. In the majority of patients, its course was free of clinical complications. The recommended dosage for mono-therapy is 1.5 mg/m² /day × 5 at 4-week intervals. Compared to the commonly used combination therapy with cyclophosphamide,adriamycin and vincristine, single-agent topotecan given as second-line therapy to patients with tumor progression or recurrence was superior in controlling tumor-related symptoms, with better subjective tolerability (non-hematological toxicity) and equivalent efficacy. Thanks to its high efficacy as monotherapy and its unique mechanism of action, topotecan is suitable for combination chemotherapy. Favorable partners are cisplatin and carboplatin, anthracyclines, etoposide, oxazaphosphorine alkylating agents and stabilizing antitubulins. A major objective in the development of an effective combination chemotherapy with topotecan is to improve the induction chemotherapy of SCLC which is urgently required (first-line). The results available thus far are encouraging, but stem mainly from phase I and early phase II studies, thereby limiting the conclusions to be drawn from them.