title: Taxanes in combination with doxorubicin in the treatment of metastatic breast cancer.
abstract: 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.
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Dieras
mesh_terms: 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
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D017239:Paclitaxel