The combination of vinorelbine with weekly trastuzumab has produced high response rate in HER2 overexpressing metastatic breast cancer (MBC). The present phase 2 study was planned to test activity of the same combination, with trastuzumab given every 3 weeks, rather than weekly.

The schedule of treatment includes vinorelbine (30 mg/m2 on days 1 & 8 every 21 days) and trastuzumab (8 mg/kg on day 1 and then 6 mg/kg every 21 days). Vinorelbine is planned for maximum 9 cycles, while trastuzumab can be continued until progression. This study is a single-stage phase 2 design, and patients eligible for response evaluation are required.

Inclusion Criteria:

• Histologically or cytologically confirmed breast cancer
• Stage IV
• No prior or not more than one prior chemotherapy for metastatic disease
• Overexpression of HER-2 (3+ on immunohistochemical exam) or amplified genetic expression of c-erbB2/neu (positive by Fish method)
• Performance status 0-2 (ECOG)

Exclusion Criteria:

• Absence of measurable disease
• Life expectancy < 3 months
• Concomitant malignancy or malignancy within previous 5 years (except basal cell or spinocellular skin cancer and in situ cervical cancer if they have been adequately treated
• Previous treatment with trastuzumab or vinorelbine
• Neutrophils < 1500/mm3 or platelets < 100000/mm3 or haemoglobin < 8 g/dl
• Creatinine > 1.5 x the value of the upper normal limit
• GOT and/or GPT > 2.5 x the value of the upper normal limit and/or bilirubin > 1.5 x the value of the upper normal limit in the absence of liver metastases
• GOT and/or GPT > 5 x the value of the upper normal limit and/or bilirubin > 3 x the value of the upper normal limit in the presence of liver metastases
• Left ventricular ejection fraction < 50% (measured by ultrasound or MUGA angiography)
• Concomitant conditions that contraindicate the use of the drugs in the protocol
• Male gender
• Pregnancy or lactation·
• Incapacity or refusal to provide informed consent
• Inability to comply with followup