A phase I study of amrubicin (AMR) and irinotecan (CPT-11) in relapsed small cell lung cancer

Abstract

18181 Background: AMR and CPT-11 have shown excellent activity in extensive small cell lung cancer (SCLC). The aim of this study was to determine the maximum tolerated dose (MTD) of amrubicin in combination with a fixed dose of CPT-11. Methods: Eligibility criteria were patients having pathologically proven SCLC, had relapsed after one or two previous chemotherapies, ECOG performance status (PS) of 0–2 and adequate organ function. Irinotecan was delivered as 50 mg/m2 on days 1 and 8, every 21 days. AMR was delivered on day 1. Doses of AMR were level 1: 80mg/ m2, level 2: 90 mg/m2 and level 3: 100 mg/ m2. Dose elevation was determined using continuous reassessment method (CRM). Tolerability was assessed after the 1st cycle. Another two cycles were conducted when disease progression or unacceptable toxicities were not observed. Results: Between June 2004 and October 2006, 18 patients were enrolled with the following characteristics: male/female, 15/3; median age, 66.3 years (range 57–61); PS 0/1/2: 4/14/0. Median number of previous treatment cycles was 5. A total of 40 courses were conducted. Grade 3/4 hematological toxicities of 1st cycle were: leukocytopenia: 67% (G3/4: 8/4); neutropenia: 89% (G3/4: 6/10), thrombocytopenia: 11% (G3/4: 1/1). Grade 3 febrile neutropenia occurred in 1 patient. Other grade 3 or greater non-hematological toxicities were observed in 4 of 40 courses (grade 3 infection in 3 courses and diarrhea in 1). In the first course, DLT was observed in 2 of 6 patients at dose level 2 (prolonged grade 4 neutropenia, febrile neutropenia), in 1 of 6 at dose level 3 (prolonged grade 4 neutropenia), MTD of amrubicin were determined by CRM to be 100 mg/m2 (level 3). Objective response was obtained in 4 patients (28%). Conclusions: This combination was well tolerated and showed activities in SCLC, though hematological toxicities were rather severe. Phase II trials are being planned in chemo naïve SCLC. No significant financial relationships to disclose.