Southwest Oncology Group S0802: A Randomized, Phase II Trial of Weekly Topotecan

Although the incidence of small-cell lung cancer (SCLC) is decreasing in the United States, perhaps because of the changing smoking patterns, there have been no significant changes in its outcome in more than 3 decades.1 The majority of patients with SCLC present with extensive stage disease and are treated palliatively with platinum-based chemother-apy. Although response rates (RRs) are high with first-line chemotherapy, relapse is nearly universal, and response to second-line chemotherapy is lim-ited and partially dependent on the duration of unmaintained remission after first-line platinum-based therapy. Patients who have a durable response to first-line chemotherapy have historically fared much better than those patients who either do not respond (ie, refractory disease) or those who have only a transient response ( 60 to 90 days).2 Topo-tecan, a camptothecin analog, is the only US Food and Drug Administration–approved agent for second-line therapy of SCLC, but activity is limited primarily to the platinum-sensitive population, and topotecan produces significant myelosuppression when given in its standard schedule (ie, daily for five days).3-5 Weekly topotecan is an alternative dosing schedule that is associated with less toxicity and sim-ilar disease control rates (DCRs).6,7 Many additional drugs have utility in the second-line setting and are included in guidelines (eg, paclitaxel,8,9 docetaxel,10 irinotecan,11 temozolomide,12 gemcitabine,13,14 vi-norelbine,15 and ifosfamide16), but their therapeutic contributions are modest at best. There clearly is a need to identify novel therapies that are effective in this setting.

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