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J Clin Oncol. 1998 Oct;16(10):3439-60.

Cytotoxic and hormonal treatment for metastatic breast cancer: a systematic review of published randomized trials involving 31,510 women.

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Laboratory of Clinical Research in Oncology, Italian Cochrane Centre, Mario Negri Institute for Pharmacologic Research, Milan.



A systematic review of randomized clinical trials (RCTs) was undertaken to assess the effectiveness of medical treatment for metastatic breast cancer.


RCTs published between 1975 and 1997 have been classified according to 12 therapeutic comparisons: (1) polychemotherapy (PCHT) agents versus single agent; (2) PCHT regimens with anthracycline versus PCHT without anthracycline; (3) other PCHT versus cyclophosphamide, methotrexate, and fluorouracil (CMF); (4) chemotherapy (CHT) with epirubicin versus CHT with doxorubicin; (5) CHT versus same CHT delivered with less intensive schedules; (6) other endocrine therapy (OET) versus tamoxifen; (7) OET plus tamoxifen versus tamoxifen alone; (8) OET versus medroxyprogesterone; (9) OET versus aromatase inhibitors; (10) OET versus megestrol; (11) endocrine therapy (ET) versus same ET at lower doses; and (12) CHT plus ET versus CHT. Tumor response rates, mortality hazards ratio (HR) and frequency of severe side effects were the outcome measures.


A total of 189 eligible trials (31,510 patients) were identified. All provided response rates and 133 (70%) data or survival curves needed for calculation of the HR. In eight of 12 comparisons, statistically significant differences for response emerged (1, 2, 3, 5, 7, 8, 11, 12); all but no. 8 favored the first term of the comparison. Overall survival analysis showed better results of (a) PCHT versus single-agent CHT (HR=0.82; 95% confidence interval [CI], 0.75 to 0.90); (b) CHT with doxorubicin versus CHT with epirubicin (HR=1.13; 95% CI, 1.00 to 1.27); (c) CHT versus the same CHT delivered with less intensive schedules (HR=0.90; 95% CI, 0.83 to 0.97); (d) ET versus the same ET at lower doses (HR=0.86; 95% CI, 0.77 to 0.97). Quality of life was measured in only 2,995 of 31,510 patients (9.5%).


Despite some evidence of effectiveness of specific regimens, the relevance of these findings is limited by the modest survival benefit and the lack of evaluation of the quality-of-life impact of these treatments.

[Indexed for MEDLINE]

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