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Topotecan: Weighing in When There Are Many Options

Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, and the Dana Farber/Harvard Cancer Center, Boston, Massachusetts, USA

Key Words. Topotecan • Ovarian cancer • Bone marrow toxicity • Second-line therapy

Correspondence: Richard T. Penson, M.R.C.P., M.D., Massachusetts General Hospital, Yawkey-9066, 55 Fruit Street, Boston, Massachusetts 02114, USA. Telephone: 617-726-5867; Fax: 617-724-6898; e-mail: rpenson{at}partners.org

The manuscript by Armstrong et al. in this issue of The Oncologist, reviewing the toxicity and efficacy of full-dose topotecan delivered as second-line therapy in individuals with small cell lung cancer or ovarian cancer, will likely serve as both the most comprehensive and the final review of this active agent delivered at the U.S. Food and Drug Administration–approved dosage and schedule. The review represents large, relative lyhomogeneous patient populations with prior platinum exposure and convincingly describes topotecan as an agent with activity that is comparable with those of all other approved drugs in this setting and a well-defined and relatively circumscribed set of toxicities. While the activity of topotecan in small cell carcinoma provides individuals with the hope for further palliation at the time of tumor recurrence, as discussed by Dr. Markman in this issue, the best use of this agent in the management of recurrent ovarian cancer is far from clear because, in part, of a growing list of approved active agents, most notably liposomal doxorubicin, gemcitabine, and weekly paclitaxel; a return to platinum; or a host of other agents such as vinorelbine, altretamine, irinotecan, docetaxel, etoposide, and others. The most pressing need is to accept that palliative therapies are designed to palliate and improve symptoms, and to move away from end points of radiologic and marker response to a focus on "clinical benefit" and clinically more meaningful end points.

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