Topotecan: a new topoisomerase I inhibiting antineoplastic agent

OBJECTIVE: To review the pharmacologic, pharmacokinetic, therapeutic, and safety aspects of topotecan, a new antineoplastic agent, and to assess its role in the treatment of cancer. DATA SOURCES: MEDLINE database English language only, January 1990-March 1998; SmithKline Beecham Pharmaceuticals; published articles, books, and abstracts. STUDY SELECTION: Studies in humans with cancer, clinical case reports, open clinical trials, and controlled clinical studies. Efficacy studies were limited primarily to trials with at least 20 evaluable patients: DATA EXTRACTION: Relevant data were extracted only from published reports. Data were obtained from studies in both articles and abstracts. Only articles written in English were reviewed. DATA SYNTHESIS: Topotecan is an effective second- or third-line therapy for patients with advanced ovarian cancer and is comparable to ifosfamide, liposomal doxorubicin, and paclitaxel. Activity in combination with other agents and as a first-line agent is yet to be determined. Limited data indicate activity in small-cell lung cancer, cancers of the breast and uterus, and in nonlymphocytic leukemia. The dose-limiting toxicity is myelosuppression. CONCLUSIONS: Topotecan is an effective second-line agent for patients with unresponsive or relapsed cancer of the ovary. It appears to be similar to other active agents in patients with this disease status. Its ultimate role in ovarian cancer and other neoplasms awaits additional evaluation in combination with other agents and as first-line therapy.

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