As the second major anticancer agent to be developed from the taxanes first found in yew trees, Taxotere (docetaxel, Rhone-Poulenc Rorer) appears to be coming into its own. Clinical trial results reported at the American Society of Clinical Oncology annual meeting in Denver show that the drug has special effectiveness as both first- and second-line therapy for metastatic breast cancer as well as for some other cancers that are difficult to treat.
"This landmark study makes a clear comparison between the two drugs that are most effective in the treatment of metastatic breast cancer," Stephen Chan, clinical oncologist at the City Hospital Breast Clinic in Nottingham, England, said of his study comparing docetaxel to doxorubicin, available from several manufacturers. "Such a comparison is crucial to defining the place of Taxotere in the treatment of metastatic breast cancer."
Commonly used agents have included doxorubicin, an anthracycline antibiotic, and paclitaxel (Taxol, Bristol-Myers Oncology), a taxane. But no head-tohead studies have been done comparing the two taxanes for this condition, an ASCO official told Drug Topics.
In Chan's randomized study in 326 women with metastatic breast cancer, he found an overall response rate of 47% for docetaxel and 32% for doxorubicin, based on an intent-to-treat analysis. This phase III trial compared docetaxel given at 100 mg/m2 with doxorubicin given at 75 mg/m2, both given three times a week. All patients had previous therapy with alkylating agents. Patients were well-balanced for age, performance status, and history of previous hormonal therapy, and 90% received the plannedfor dose intensity in both arms of the study. About 80% in both arms had visceral disease.
Chan said the primary endpoint of the study was to look at time-to-disease progression, with preliminary analysis in the first 200 patients showing an eight-week difference in favor of docetaxel. Final analysis of this endpoint should be available in about six months. In terms of toxicity, the drugs were alike, but there were also some striking differences, according to Chan. Myelosuppression and neutropenia were about the same in both arms, and adverse events as a reason for discontinuing therapy were roughly equivalent in the two arms.
However, cardiac toxicity was the major adverse side effect for doxorubicin, with 13 patients affected, two of whom died, according to Chan. The cumulative dose of the drug received by these patients, none of whom had known prior heart disease, was between 350 and 450 mg/m2. With docetaxel, the major adverse side effects were a reversible neuropathy, which resulted in the discontinuation of treatment in seven patients, and fluid retention, which caused three patients to drop out. …