At the 24th Annual San Antonio Breast Cancer Symposium, researchers reported a 78% overall response rate in a phase II trial of vinorelbine (Navelbine) plus trastuzumab(Drug information on trastuzumab) (Herceptin) in women with HER2-positive metastatic breast cancer. According to FDA-approved labeling, vinorelbine is not indicated for metastatic breast cancer.
"The response rate from our multicenter study and a previously reported response rate of 75% from an earlier single-site trial are both very encouraging," said Mohammed Jahanzeb, md, research director of the Boca Raton Comprehensive Cancer Center and professor of biomedical research at Florida Atlantic University, referring to an earlier investigation at the Dana-Farber Cancer Institute in Boston (J Clin Oncol 14:2722-2730, 2001).
The phase II trial investigated the safety and efficacy of trastuzumab and vinorelbine as first-line therapy for metastatic breast cancer in women with tumors that overexpress the HER2 protein. The trial enrolled 40 patients who received weekly intravenous doses of trastuzumab and vinorelbine administered over 4-week cycles. After receiving at least two cycles, 37 patients were evaluated for a response. A total of 4 complete and 25 partial responses were observed for an overall response rate of 78%. Disease progression developed in four patients, and four remained stable.
Tolerability With Combination
After a cumulative total of 313 cycles, significant toxicity (consisting of grade 4 neutropenia) was seen in 30% of patients, in 14% of cycles. Grade 3 neutropenia occurred in 50% of patients, in 20% of cycles. One patient was hospitalized with neutropenic fever. No grade 3/4 nausea, vomiting, heart disturbance, or hair loss was reported. Grade 3/4 nonhematologic toxicity consisted of grade 3 fatigue in one patient, grade 4 fatigue in one patient, and grade 3 neurotoxicity in one patient. The addition of vinorelbine did not appear to change the side-effect profile of trastuzumab, which was also shown to be well tolerated.
"We didn’t want to increase side effects in our efforts to potentially increase efficacy, so in selecting an agent to use in combination with Herceptin, which is well tolerated, we chose to study Navelbine," said Dr. Jahanzeb.