HOUSTON-A weekly regimen of paclitaxel (Taxol) and 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.
HOUSTONA weekly regimen of paclitaxel (Taxol) and 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.