Topotecan in the treatment of gynecologic cancer

Topotecan (Hycamtin; SmithKline Beecham Pharmaceuticals, Philadelphia, PA), a derivative of the topoisomerase I inhibitor camptothecin, was approved by the Food and Drug Administration in May 1996 for the salvage treatment of ovarian cancer. It has shown promising clinical activity in a variety of solid tumors, including cervical cancer. Phase II and III trials in patients with cisplatin-resistant ovarian cancer have been conducted using a regimen of a single 30-minute intravenous topotecan infusion (1.5 mg/m²/d) for 5 days, repeated every 21 days. Significant responses, both partial and complete, have been observed in 14% to 21% of patients, with stable disease achieved in as many as 61%. In advanced or recurrent cervical cancer, partial response or stable disease was achieved in 59% of phase II trial patients. Myelosuppression is the major dose-limiting toxicity associated with topotecan. In general, the severity of myelosuppression shows a positive correlation to the magnitude of exposure to topotecan. Support with granulocyte colony-stimulating factor may partially ameliorate myelosuppressive effects.