A phase I study of amrubicin and carboplatin for previously untreated patients with extensive stage small-cell lung cancer

Abstract

19070 Background: Amrubicin (AMR) and cisplatin are active in the treatment of small cell lung cancer (SCLC), and carboplatin (CBDCA) is an analogue of cisplatin with less nonhematological toxicity. However, the appropriate dose of AMR and CBDCA combination chemotherapy for previously untreated patients with extensive stage SCLC has not been established. This phase I trial aimed to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT). Methods: Eligibility criteria were chemotherapy-naïve extensive stage SCLC patients (pts), performance status (PS) 0–1, age ≤ 75, and adequate hematological, hepatic and renal function. Pts received escalating AMR dose under a fixed target AUC = 5 of CBDCA (Chatelut formula, Jaffe method). AMR and CBDCA were administered i.v. infusion on days 1, 2 and 3, and day 1. The initial dose of AMR was 30 mg/m2, and the dose was escalated to 35 and 40. DLT was defined as grade (G) 4 leukopenia (L) or neutropenia (N) lasting ≥ 4 days, G4 thrombocytopenia (T), febrile neutropenia or non-hematologic toxicity ≥ G3. Therapy was repeated in every 4 weeks. Results: 16 pts were enrolled and 15 eligible pts were evaluated. Pts’ characteristics: male/female = 15/0; PS 0/1 = 2/13; median age (range) = 67 (49–75); IIIB/IV = 6/9. Toxicities were in Table. One of 6 pts in level 1, 1 of 6 in level 2, and 3 of 3 in level 3 experienced DLT. Evaluation of responses were: 2CR, 9PR, 3SD and 1PD (RR 73%). Conclusions: The MTD dose of AMR and CBDCA were determined 40 mg/m2 and AUC=5. The DLT were neutropenia, thrombocytopenia, leucopenia, febrile neutropenia, and liver dysfunction. The dose of AMR 35 mg/m2 and CBDCA AUC = 5 was recommended in this study. Toxicities Level Amrubicin Carboplatin Pts G3/4L G3/4N G3/4T Liver ≥ 3 DLT 1 30 AUC=5 6 1/1 4/1 1/0 1 1 2 35 AUC=5 6 2/0 4/2 2/1 0 1 3 40 AUC=5 3 1/2 0/3 1/1 0 3 No significant financial relationships to disclose.