HOUSTON—A weekly regimen of paclitaxel(Drug information on paclitaxel) (Taxol) and trastuzumab(Drug information on trastuzumab) (Herceptin) produced evidence of enhanced antitumor activity in patients with metastatic breast cancer and HER-2 overexpression, according to preliminary results from an ongoing phase II trial.
The weekly combination therapy has achieved a response rate of almost 80% in patients whose tumors are HER-2 positive by two different tests. Moreover, half of HER-2 negative patients have responded to the regimen, Francisco Esteva, MD, reported at the San Antonio Symposium.
“These results show that weekly paclitaxel-Herceptin is an effective therapy for HER-2-overexpressing tumors,” said Dr. Esteva, of M.D. Anderson Cancer Center. “However, the efficacy of the regimen in HER-2-negative patients remains to be defined.”
The rationale for the combination comes from evidence that the mono-clonal antibody Herceptin enhances paclitaxel activity in HER-2-expressing tumors, Dr. Esteva said. Additionally, several recent studies have demonstrated that weekly administration of paclitaxel might be better tolerated and possibly more effective than conventional dosing once every 3 weeks.
100 Patients Enrolled
Investigators at M.D. Anderson and Memorial Sloan-Kettering Cancer Center have enrolled 100 patients in the trial, and Dr. Esteva reported preliminary efficacy data for 62 patients.
The investigators have also compared methods for assessing HER-2 expression as a means of predicting response to treatment: two polyclonal antibody tests, two monoclonal antibodies, and fluorescence in situ hybridization (FISH).
Dr. Esteva said that 84% of the patients had liver or lung metastases, and 85% had a history of chemotherapy for metastatic disease: 68% had prior anthracycline therapy, and 15% had received taxane-based treatment.
The study regimen consists of paclitaxel at a dose of 90 mg/m2 and Herceptin given as a 4 mg/kg loading dose followed by 2 mg/kg over 30 minutes. The combination is repeated on a weekly basis and given indefinitely until disease progression or dose-limiting toxicity.
The overall response rate was about 60%, including 50% among HER-2-negative patients. The highest response rate was 78%, seen in patients who tested positive for HER-2 by both the HercepTest polyclonal assay and the TAB250 monoclonal antibody.
The Cancer and Leukemia Group B recently modified the protocol for an ongoing clinical trial (CALGB 9840) to permit Herceptin therapy in HER-2-positive patients with metastatic breast cancer who have been randomized to weekly paclitaxel or to paclitaxel every 3 weeks. Patients in the trial with HER-2-negative tumors will be further randomized to Herceptin or no Herceptin, Dr. Esteva said.
