Taxanes in combination with doxorubicin in the treatment of metastatic breast cancer.
Given their high level of activity when used as single agents in metastatic breast cancer, the combination of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) with doxorubicin is a logical development in the search for regimens that will improve prognosis in this disease. In a phase I trial conducted at the Institut Curie and Hospital Paul-Brousse (Paris, France), 42 women with previously untreated metastatic breast cancer received a total of 286 cycles of the combination at six dose levels. Prophylactic steroids and H1 and H2 blockers were given. The maximum tolerated dose was 85 mg/m2 docetaxel plus 50 mg/m2 doxorubicin. Except for neutropenia, no grade 3-4 or severe nonhematologic toxicities were seen. The incidence of fluid retention was low: moderate toxicity in only 19% of patients and no severe cases. No cases of congestive heart failure or symptomatic decrease in left ventricular ejection fraction occurred (median cumulative doxorubicin dose, 392 mg/m2; range, 240 to 559 mg/m2). High activity was observed at all dose levels. For patients receiving one of the four highest dose levels, the overall response rate was 81% (95% confidence intervals, 63% to 93%); comparable levels of response were seen at all disease sites. The doses recommended for phase II/III studies of this active and well-tolerated combination are either 50 mg/m2 doxorubicin plus 75 mg/m2 docetaxel or 60 mg/m2 of both drugs. Encouraging response rates also have been seen in studies in which paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was combined with doxorubicin, although cardiotoxicity was a significant factor in some studies.
Dieras
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Department of Medical Oncology, Institut Curie, Paris, France.
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D043823:Taxoids
D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D017239:Paclitaxel