Phase I study of amrubicin hydrochloride and cisplatin in patients previously treated for advanced non-small cell lung cancer

Objective: A single-center phase I trial was designed to determine both the dose-limiting toxicities and the maximum tolerated dose (MTD) for amrubicin hydrochloride in combination therapy with cisplatin for advanced non-small cell lung cancer (NSCLC) patients with prior chemotherapy. Methods: Eligible patients received amrubicin and cisplat in on days 1 through 3 every 3 or 4 weeks. Cisplatin was administered at a fixed dosage of 20 mg/m² while the administered dose of amrubicin was started at 20 mg/m². Each group comprised 3 or 6 patients. When dose limiting toxicities were noted in three or more of six patients at a particular level, that level was estimated to be the MTD. Results: Fifteen patients were enrolled in this study, including 5 males and 10 females, with a median age of 57. The dose limiting toxicities included grade 4 neutropenia which lasted 4 or more days and febrile neutropenia. The non-hematologic toxicities were well managed and rarely severe. The MTD of amrubicin in this combination regimen was estimated to be 30 mg/m².A partial response was observed in 4 of 15 patients (27%). Conclusions: The recommended dose was thus determined to be 25 mg/m² amrubicin with 20 mg/m² cisplatin for 3 consecutive days. A phase II study is currently underway.