Docetaxel (Taxotere) plus doxorubicin-based combinations: the evidence of activity in breast cancer.
The high individual response rates of doxorubicin and docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) as single agents in breast cancer and their lack of cross-resistance provide the rationale for investigation of the combination of these two uniquely acting agents. A dose-finding study defined the recommended doses for the combination given every 3 weeks as docetaxel 75 mg/m2 plus doxorubicin 50 mg/m2, or docetaxel 60 mg/m2 plus doxorubicin 60 mg/m2. Phase II studies conducted with these doses in first-line treatment of metastatic breast cancer patients resulted in overall response rates ranging between 57% and 77% with long durations of response. The high response rates were maintained in patients with unfavorable prognostic features, such as multiple metastatic disease sites, visceral involvement, and prior exposure to adjuvant chemotherapy. Without prophylactic G-CSF, grade 3/4 neutropenia and febrile neutropenia were the predominant hematologic toxicities. However, infectious complications occurred infrequently. The nonhematologic toxicities of docetaxel and doxorubicin in combination are low in frequency and mild in severity. Additionally, the incidence of congestive heart failure was no greater than that expected with single-agent doxorubicin. The safety and efficacy results of these phase I and II trials appear to be confirmed in a randomized phase III trial comparing docetaxel plus doxorubicin versus doxorubicin plus cyclophosphamide in first-line metastatic breast cancer. Preliminary results reveal a superior overall response rate of 60% with docetaxel plus doxorubicin versus 47% with doxorubicin plus cyclophosphamide (p = .008). Time to disease progression and overall survival results are awaited. The results of these trials, in addition to others being conducted in the adjuvant and the neoadjuvant settings, will establish the ultimate place in therapy for the docetaxel and doxorubicin combination in the management of patients with breast cancer.
Nabholtz
J M
JM
Northern Alberta Breast Cancer Program, Cross Cancer Institute, Edmonton, Canada.
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D043823:Taxoids
D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D017239:Paclitaxel