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Phase I Study of Vinorelbine and Carboplatin Combination in Patients with Taxane and Anthracycline Pretreated Advanced Breast Cancer

Aim: To define the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of the carboplatin-vinorelbine combination in pretreated patients with advanced breast cancer. Patients and Methods: Patients with histologically confirmed metastatic breast cancer relapsing or progressing after prior taxane and anthracycline containing chemotherapy were enrolled. Cohorts of 3–6 patients were treated at successive dose levels (DLs) with escalated doses of carboplatin [range, area under the curve (AUC) 4–6] on day 1 and vinorelbine (range, 20–35 mg/m2) on days 1 + 8 recycled every 28 days. Results: Twenty-seven patients with a median age of 58 years and performance status (WHO) of 0–2 were treated at 6 DLs. All patients were assessable for toxicity and 20 for response. DLT was reached at carboplatin 6 AUC and vinorelbine 35 mg/m2, and therefore, this was considered as the MTD. Prophylactic G-CSF administration could not allow further dose escalation. The recommended dose for further phase II testing was defined at carboplatin 6 AUC on day 1 and vinorelbine 30 mg/m2 on days 1 and 8. Among 98 administered treatment cycles 41 (42%) and 7 (7%) were complicated with grades 3 and 4 neutropenia and thrombocytopenia, respectively. Nonhematologic toxicities included grade 2 peripheral neuropathy in 3 cycles and grades 2 and 3 fatigue in 32 (32%). Conclusion: The present study determined the feasibility of the combination of carboplatin at AUC 6 (day 1) and vinorelbine at 30 mg/m2 (days 1 and 8 ) without G-CSF support in patients with taxane and anthracycline pretreated advanced breast cancer. Phase II studies at these doses should follow in order to determine the activity of the regimen.