A multicenter phase I-II trial was carried out with the aim of identifying the dose-limiting toxicity and the maximum tolerated dose of vinorelbine (VNR) in combination with pegylated liposomal doxorubicin at a dose of 20 mg/m2 every 15 days in patients with metastatic breast carcinoma. In the phase I part of the trial, VNR was given at a dose of 20 mg/m2 every 15 days to a group of 3 patients. In absence of unacceptable toxicity, VNR was escalated to 25, 30, and 35 mg/m2 for subsequent groups of 3 patients, until the dose-limiting toxicity was reached. No case of palmar-plantar erythrodysesthesia was recorded in these patients. Grade 4 neutropenia, grade 3 thrombocytopenia, and grade 3 mucositis were the dose-limiting toxicities recorded in patients treated with VNR 35 mg/m2. These side effects caused a substantial decrease in programmed dose intensity. Therefore 30 mg/m2 was considered the maximum tolerated dose of VNR in combination with pegylated liposomal doxorubicin 20 mg/m2, both given every 15 days. These dosages were employed for the treatment of further 18 patients included in phase II of the study. The overall response rate, calculated according to an intention to treat analysis, was 63% (95% CI: 44–80%), with 2 patients achieving a complete response. The median time to progression was 7.0 months or more (range 2–14 months). Median duration of objective responses was 8.4 months or more. The duration of the 2 complete responses was 9 and 14 months, respectively. Median duration of survival was 16.0 months or more (range from 4.0 to ≧24.0). Toxicity was generally mild and easily manageable. Neutropenia and mucositis were the most frequently recorded side effects. A case of palmar-plantar erythrodysesthesia was recorded in phase II of the study. In conclusion, the maximum tolerated dose of VNR in association with pegylated liposomal doxorubicin is 30 mg/m2 on a bimonthly schedule. Moreover, the combination of VNR and pegylated liposomal doxorubicin is active against metastatic breast carcinoma and is associated with a good toxicity profile. Further studies with this combination regimen are warranted.

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