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Clinical Guidelines for Managing Topotecan-Related Hematologic Toxicity

Johns Hopkins Oncology Center, Baltimore, Maryland, USA

Correspondence: Seamus O'Reilly, M.D., Ph.D., Johns Hopkins Oncology Center, 600 North Wolfe Street, Room 137, Baltimore, Maryland 21287-8934, USA. Telephone: 410-614-4192; Fax: 410-955-0125; email: oreilse{at}welchlink.welch.jhu.edu

Purpose: Topotecan, a semisynthetic water-soluble camptothecin analog, was recently approved as a second-line treatment for women with ovarian cancer. In clinical trials, hematologic toxicity has been the predominant toxicity associated with its use. The purpose of this article is to provide guidelines on the clinical management of these toxicities.

Methods: The guidelines on the management of hematologic toxicities associated with topotecan therapy for advanced ovarian cancer patients were established through a review and analysis of phase I, II, and III clinical trials.

Results: In phase I studies, noncumulative neutropenia was the predominant toxicity associated with topotecan therapy. In subsequently conducted phase II trials, thrombocytopenia related to prior carboplatin and alkylating agent therapies has become a prominent toxicity, and neutropenia has been more severe than anticipated from phase I studies. The risk for both toxicities relates to the extent of prior myelosuppressive chemotherapy and to renal impairment. These toxicities can be managed through the identification of high-risk patients and implementation of appropriate prophylactic measures. Such measures include dose reductions or the use of hematopoietic growth factors. For patients with persistently low blood cell parameters, transfusion therapy remains a viable option.

Conclusion: Hematologic toxicities associated with topotecan therapy are noncumulative. Consequently, once a dosing regimen is established, toxicity patterns are predictable. Pretreatment assessment of the nature and toxicities of prior therapy and renal function should assist the clinician in preventing complications caused by the myelosuppressive effects of topotecan therapy.

Key Words. Topotecan • Topoisomerase I inhibitor • Chemotherapy • Ovarian cancer

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