A phase I study of weekly oral topotecan in patients (pts) with relapsed small cell lung cancer (SCLC).

Abstract

7081 Background: Oral topotecan represents a standard treatment in pts with relapsed SCLC. Oral topotecan 2.3 mg/m2/day for 5 days, repeated every 3 weeks is associated with severe hematologic toxicity in more than 50% of pts. The weekly administration of oral topotecan has not been studied. A phase I trial was conducted to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of oral topotecan administered weekly in patients with relapsed SCLC. Methods: Pts with relapsed SCLC were treated with oral topotecan on days 1, 8, and 15, every 28 days. The dose was escalated in 0.5 mg/m2 increments from the starting dose of 3 mg/m2 until the MTD was reached. DLTs were defined as grade 4 neutropenia, febrile neutropenia, grade 4 thrombocytopenia, non-hematologic toxicity ≥ grade 3, or any toxicity precluding the administration of treatment on days 8 or 15 of the 1st cycle or on day 1 of the 2nd cycle. Results: Eighteen pts (median age, 56 years, 77.8% male) were enrolled. Performance status was 0-1 in 94.4%. Thirteen (72.2%) pts [6 (46.2%) with sensitive and 7 (53.8%) with refractory relapse] received oral topotecan as 2nd line and 5 (28.2%) as ≥3rd line treatment. Three DLTs among 6 pts were observed at the 4.5 mg/m2 dose level (grade 3 neutropenia and grade 2 thrombocytopenia on day 15 of the 1st cycle in 1 pt, grade 2 neutropenia on day 15 of the 1st cycle in 1 pt, and grade 2 neutropenia on day 1 of the 2nd cycle in 1 pt). The MTD was determined to be 4 mg/m2 (1 of 6 pts experienced a DLT consisting of grade 3 neutropenia on day 15 of the 1st cycle). Hematologic and non-hematologic adverse events included neutropenia (grade 2 in 16.7%, grade 3 in 11.1%), anemia (grade 2 in 27.8%, grade 3 in 5.6%) thrombocytopenia (grade 2 in 16.7%), nausea-vomiting (grade 2 in 5.6%), diarrhea (grade 2 in 5.6%), neurotoxicity (grade 2 in 5.6%) and fatigue (grade 2 in 33.3%, grade 3 in 11.1%). The response rate was 11.1%, the median time to tumor progression 2.3 months (range, 1.1-10.0) and the median overall survival 5.1 months (range, 1.5-10.2). Conclusions: The recommended phase II dose of weekly oral topotecan in pretreated pts with SCLC is 4 mg/m2 on days 1, 8 and 15 every 28 days.