Phase I study of amrubicin and vinorelbine in non-small cell lung cancer previously treated with platinum-based chemotherapy

Background  Combination chemotherapy comprising amrubicin and vinorelbine as a second-line therapy for advanced non-small cell lung cancer (NSCLC) has not been fully evaluated. To determine the maximum tolerated dose (MTD) and recommended dose (RD), the present phase I study examined patients with advanced NSCLC. Methods  The subjects were nine patients with histologically confirmed advanced NSCLC, Eastern Cooperative Oncology Group performance status 0–1, prior platinum-based first-line chemotherapy, and measurable or evaluable lesions. Treatment consisted of five dose levels, with amrubicin 35–45 mg/m² administered as a 5-min intravenous infusion on days 1–3 and vinorelbine 15–25 mg/m² given as a 1-h intravenous infusion on days 1 and 8, every 3 weeks. Results  All patients had received carboplatin and paclitaxel as first-line therapy. Dose-limiting toxicity (DLT) was seen in two of six patients (febrile neutropenia and deep vein thrombosis ) at level 1, allowing us to conduct level 2. At level 2, all three patients experienced DLT (leucopenia ≥4 days in one patient; febrile neutropenia in three patients; and infection in two patients), and this level was determined as the MTD. Subsequently, level 1 (amrubicin 35 mg/m² and vinorelbine 15 mg/m²) was defined as the RD. Responses in the nine patients included a partial response in one patient and stable disease in four patients. Conclusion  As second-line therapy, the RD of the combination of amrubicin and vinorelbine is 35 mg/m² and 15 mg/m², respectively. Further study should proceed to clarify the efficacy of this regimen.