Phase I study of amrubicin (AMR) for patients (pts) with previously treated small cell lung cancer (SCLC)

Abstract

18209 Background: Amrubicin, a totally synthetic 9-amino-anthracycline, has been demonstrated to have excellent antitumor activity against previously untreated SCLC. However, severe hematological toxicities were observed in previously treated SCLC when given at doses of 40 to 45 mg/m2, days 1–3. We sought to determine the maximum tolerable dose (MTD) and toxicity of amrubicin for pts with previously treated SCLC. Methods: Pts with confirmed SCLC, ECOG PS 0–1, and 20 to 74 years of age, with a history of receiving one or two regimens were eligible for the study. Pts were divided into two groups. Group R (-) consisted of pts without history of radiotherapy except prophylactic cranial irradiation. Group R (+) consisted of pts with history of irradiation up to two fields including thoracic radiotherapy. AMR was initially given at 35 mg/m2, iv, days 1–3, every 3 weeks in both groups. The dose was then increased to 40 and 45 mg/m2. Three pts were treated at each dose level in the absence of a dose limiting toxicity (DLT). All pts received prophylactic hG- CSF between days 8–13. DLT was defined as neutrophil nadir <500/μL lasting more than 4 days, neutropenic fever and neutrophil nadir <1000/μL, platelet nadir <20,000/μL or ≥ grade 3 non-hematologic toxicities. Results: Fourteen pts were enrolled, 10m/4f. The median age was 62 years (range 34–82). Two of 6 pts in the first cohort in group R (-) had dose-limiting neutropenia. The dose escalation is ongoing. Three pts in the first cohort in group R (+) had no dose-limiting toxicities. A subsequent 5 pts were treated at dose-level 2, and 3 pts had dose-limiting neutropenia. The MTD in group R (+) was 40 mg/m2. A response rate of 62% was observed. Median survival time was 12 months. No treatment-related death was observed. Conclusions: The MTD in group R (-) was not determined. The MTD in group R (+) was determined as 40 mg/m2. Further data will be presented. No significant financial relationships to disclose.