Topotecan: An Oncologist's View

Topotecan (Hycamtin(R)) is a topoisomerase I inhibitor which demonstrated a wide spectrum of antitumor activity in preclinical models. During phase I assessment, evidence of activity was most promising when topotecan was administered on an i.v. daily x 5 schedule and a dose of 1.5 mg/m(2)/day was selected for phase II/III evaluation. This regimen has been shown to have activity in a wide range of tumor types, including recurrent ovarian cancer, relapsed small cell lung cancer (SCLC), non-small cell lung cancer, colon cancer, and breast cancer, as well as hematological malignancies. In patients with ovarian cancer who had failed standard therapy, topotecan demonstrated response rates of 13% to 25%, with median times to progression of 12 to 19 weeks. Compared with paclitaxel, the response rates were similar, 20.5% and 14.0%, respectively, as were median times to progression (19 weeks for topotecan versus 15 weeks for paclitaxel). Results in recurrent SCLC have also been encouraging. Patients sensitive to previous chemotherapy have shown response rates of 19% and 39%, and even patients resistant or refractory to previous chemotherapy have had responses of 3% and 7%. Survival ranged from 20 weeks in refractory disease to 12 months in both sensitive and resistant/refractory disease combined. The safety profile of topotecan is well established. The principal toxicity is noncumulative myelosuppression, and serious sequelae are uncommon. Nonhematological toxicities are generally mild. The use of topotecan in combination regimens is promising, although clinical results are currently at an early stage. To date, topotecan has demonstrated its activity in recurrent ovarian cancer and offers a valuable addition to treatment options in relapsed SCLC.