84 Phase II study of topotecan in refractory and sensitive small cell lung cancer (SCLC)

Topotecan (T) is a semisynthetic-camptothecin analog with specific topoisomerase I inhibitory effect and preclinical activity in a broad range of tumors including SCLC. A multicentre Phase II study to assess activity and toxicity in pretreated SCLC patients (pts) has recently been closed. Two groups of pts were enrolled: “sensitive” (S) pts who responded to 1st line chemotherapy (CT) but progressed 2 d×5 q3 weeks until progression or excessive toxicity. A total of 94 eligible pts were entered and 353 courses (crs) and 87 pts (48 R, 39 S) have been evaluated. Pts characteristics are: median age 59, median PS 1, median duration of prior CT 4 months and median No. of prior drugs 3. In 39 S pts 5 CR and 13 PR were observed (46%), in 48 R pts 1 CR and 3 PR (8%). Toxicity (NCI grading) was mainly hematological. Leucopenia, although short lived was common with gr. III and IV neutropenia occurring in 78% of crs. Nine pts developed infections, 2 died while neutropenic. Gr. III and IV thrombocytopenia was observed in 29% of crs and 54% of pts. Anemia gr. III and IV occurred in 29% of pts. Non-hematological toxicity was mild. Asthenia was observed in 35% of crs with only 3 gr. IV episodes. Diarrhea was reported in 12 crs (1 gr. III), vomiting gr. III in only I crs. Toxicity required dose reduction in 10% of courses, treatment delay in 18% of crs. Preliminary results indicate that the concept of testing new drugs in S and R pts is feasible, that T has significant activity, especially in S, but even in R pts, and that toxicity is manageable. The study is closed for patient entry and final results will be available in October 1995.