Topotecan as second-line therapy for ovarian cancer: dosage versus toxicity

In this issue of The Oncologist, Armstrong et al. present an analysis of the use of topotecan (Hycamtin; GlaxoSmithKline, Philadelphia, http://www.gsk.com) in the second-line treatment of both ovarian cancer and small cell carcinoma of the lung. This cytotoxic agent has clearly been demonstrated to be a useful drug in a population of patients with both of these conditions. However, the description of the nature of the toxicity, as stated in the manuscript, must be questioned along with comments made regarding the relative toxicity of alternative cytotoxic agents frequently used in similar settings. The purpose of this discussion absolutely is not to negate the unquestioned, demonstrated usefulness of topotecan as second-line therapy in ovarian cancer but rather to point out that the U.S. Food and Drug Administration-approved dose level of 1.5 mg/m(2) per day x 5 days can cause substantial and highly clinically relevant bone marrow toxicity. Whether this toxicity, which can result in a level of fatigue that may cause responding patients to discontinue treatment, should simply be labeled "excessive" rather than "cumulative" appears to be a matter of semantics rather than an important distinction. Whether delivery of a lower dose of topotecan (1 mg/m(2)-1.25 mg/m(2) per day x 5 days) will essentially eliminate concern for the development of severe clinically relevant marrow toxicity is uncertain, but the risk will certainly be substantially reduced.