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 (Herceptin) in women with HER2-positive metastatic breast cancer. According to FDA-approved labeling, vinorelbine is not indicated for metastatic breast cancer.
At the 24th Annual San Antonio Breast Cancer Symposium,researchers reported a 78% overall response rate in a phase II trial ofvinorelbine (Navelbine) plus trastuzumab (Herceptin) in women with HER2-positivemetastatic breast cancer. According to FDA-approved labeling, vinorelbine is notindicated for metastatic breast cancer.
"The response rate from our multicenter study and a previously reportedresponse rate of 75% from an earlier single-site trial are both veryencouraging," said Mohammed Jahanzeb, md, research director of the BocaRaton Comprehensive Cancer Center and professor of biomedical research atFlorida Atlantic University, referring to an earlier investigation at theDana-Farber Cancer Institute in Boston (J Clin Oncol 14:2722-2730, 2001).
The phase II trial investigated the safety and efficacy of trastuzumab andvinorelbine as first-line therapy for metastatic breast cancer in women withtumors that overexpress the HER2 protein. The trial enrolled 40 patients whoreceived weekly intravenous doses of trastuzumab and vinorelbine administeredover 4-week cycles. After receiving at least two cycles, 37 patients wereevaluated for a response. A total of 4 complete and 25 partial responses wereobserved for an overall response rate of 78%. Disease progression developed infour patients, and four remained stable.
Tolerability With Combination
After a cumulative total of 313 cycles, significant toxicity (consisting ofgrade 4 neutropenia) was seen in 30% of patients, in 14% of cycles. Grade 3neutropenia occurred in 50% of patients, in 20% of cycles. One patient washospitalized with neutropenic fever. No grade 3/4 nausea, vomiting, heartdisturbance, or hair loss was reported. Grade 3/4 nonhematologic toxicityconsisted of grade 3 fatigue in one patient, grade 4 fatigue in one patient, andgrade 3 neurotoxicity in one patient. The addition of vinorelbine did not appearto change the side-effect profile of trastuzumab, which was also shown to bewell tolerated.
"We didn’t want to increase side effects in our efforts to potentiallyincrease efficacy, so in selecting an agent to use in combination withHerceptin, which is well tolerated, we chose to study Navelbine," saidDr. Jahanzeb.
In the earlier Dana-Farber study, investigators reported responses in 30 of40 patients who received concurrent weekly doses of vinorelbine and trastuzumab,for an overall response rate of 75%. Grade 3/4 neutropenia occurred in 43% ofpatients. Neutropenia was the only reported grade 4 toxicity associated with thetreatment. No patients had symptomatic heart failure.
Dr. Jahanzeb said that the present multicenter trial suggests a possiblesynergistic effect between vinorelbine and trastuzumab in the treatment ofmetastatic breast cancer. He called for additional phase III trials.
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