Weekly herceptin with navelbine in chemonaïve patients with HER2 positive metastatic breast cancer: A phase II multicenter trial

Herceptin (H) and Navelbine (N) are well tolerated agents with pre-clinical synergy and documented efficacy in breast cancer as recently reported by Burstein et. al. (J Clin Oncol 19: 2722-2730). Objectives: This phase II multicenter trial was initiated to evaluate the efficacy and safety of H+N as first-line treatment for HER2 overexpressing metastatic breast carcinoma patients with measurable disease. Methods: Eligible women were treated with weekly IV doses of H (4mg/kg loading dose, then 2mg/kg) and N (30mg/m²) without a break, with 4 weeks comprising a cycle. Results: As of May 10, 2001, all of the planned 40 patients have been entered. Patient characteristics are: median age 51 years (range 30-82); prior adjuvant chemo 30%; prior hormonal therapy 32%; visceral metastases 60%. Thirty two patients are evaluable for response, having received at least 2 cycles. Three CRs and 20 PRs have been observed with an overall objective response rate of 72%, while 5 patients are stable and 3 progressed. Median time to response was 8 weeks. To date, a total of 225 cycles have been administered (median 4, range 1 to 28) with dose delays in 30% of the cycles Grade 4 toxicity was limited to neutropenia experienced by 30% of patients in 10% of cycles, while 50% of patients experienced Grade 3 neutropenia in 20% of cycles. Four patients were hospitalized with fever (1 neutropenic, 1 line sepsis, 1 with tuberculosis, 1 with pneumonia), 1 patient with hematura (due to over anti-coagulation from coumadin) and 1 patient with pulmonary embolism. Non-hematologic toxicity of fatigue was observed as grade 3 in one patient and grade 4 in another patient. One patient experienced Grade 3 neurotoxicity. No severe nausea, vomiting, cardiotoxicity, or alopecia has been reported. Conclusion: These data from a multicenter trial suggest that H+N is well tolerated and very active in this patient population, and validate the previously reported single institution experience.