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
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.