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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Dose-finding study of weekly docetaxel, anthracyclines plus fluoropyrimidines as first-line treatment in advanced breast cancer.

BACKGROUND: The efficacy and safety of prolonged fluoropyrimidines, either intravenously or orally, prompted their integration with taxanes and anthracyclines in the treatment of advanced breast cancer (ABC). We conducted three subsequent dose-finding studies on first-line chemotherapy in ABC with anthracyclines, either epirubicin ( E) or doxorubicin (A), and docetaxel (T), both given on days 1 and 8 every 3 weeks, plus continuous infusion (CI) 5-fluorouracil ( F) or capecitabine (X). PATIENTS AND METHODS: Sixty-two patients (37% dominant visceral disease, 48% locally advanced disease, 45% two or more sites involved), received different doses of T (60--80 mg/m(2)), A (40--50 mg/m(2)) or E (60--90 mg/m(2)) and X (1,650 and 2,000 mg/m(2)), or CI F at a fixed daily dose of 200 mg/m(2). Cardiac function was monitored at baseline and then every four cycles by echocardiography. RESULTS: The median number of cycles per patient with all regimens was four (range one to eight). Haematological and gastrointestinal toxicity defined the maximum tolerated doses, at T-80/E-90 mg/m(2) with TEF, T-70/A50/X-2,000 mg/m(2) with TAX and T-70/E-80/X-1,650 mg/m(2) with TEX. Two patients treated with TEF developed transient cardiac toxicity (dilatative cardiomyopathy and coronary subtotal stenosis requiring stenting) after cumulative E doses of 400 mg and 1,100 mg/m(2), respectively. Fifty-nine patients were evaluable for response; the overall response rates (ORR) were comparable between regimens (54% with TEF, 71% with TAX and 86% with TEX), with an 81% ORR in 31 patients with locally advanced disease. CONCLUSIONS: The addition of fluoropyrimidines to weekly, intermittent ET is well tolerated and active in ABC.[1]


  1. Dose-finding study of weekly docetaxel, anthracyclines plus fluoropyrimidines as first-line treatment in advanced breast cancer. Pagani, O., Sessa, C., Nolè, F., Munzone, E., Crivellari, D., Lombardi, D., Thürlimann, B., Hess, D., Graffeo, R., Ruggeri, M., Longhi, S., Goldhirsch, A. Ann. Oncol. (2005) [Pubmed]
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