Planned intensification of chemotherapy with cisplatin and doxorubicin increased received dose intensity and resulted in a statistically significant increase in favorable histologic response rate, but not in increased progression-free or overall survival. Our results call into question the use of histologic response as a surrogate outcome measure in trials of this disease.

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A B S T R A C T PurposeThis phase III randomized open-label clinical trial was designed to evaluate the efficacy and safety of the steroidal aromatase inactivator exemestane versus the antiestrogen tamoxifen as first-line treatment for metastatic breast cancer (MBC) in postmenopausal women. Patients and MethodsThe study was conducted at 81 centers and enrolled postmenopausal patients with measurable hormone-sensitive metastatic or locally advanced breast cancer. Prior adjuvant chemotherapy and/or tamoxifen were allowed. One previous chemotherapy regimen and no prior hormone therapy for advanced disease were permitted. Patients were randomly assigned to receive exemestane 25 mg or tamoxifen 20 mg orally once daily until disease progression or unacceptable toxicity occurred. ResultsA total of 371 patients enrolled at 79 sites (182 exemestane, 189 tamoxifen) were included in the analysis. Both treatments were generally well tolerated without major toxicity. Overall response rate was greater for exemestane than for tamoxifen treatment (46% v 31%; odds ratio ϭ 1.85; 95% CI, 1.21 to 2.82; P ϭ .005). Median progression-free survival (PFS) was longer with exemestane (9.9 months; 95% CI, 8.7 to 11.8 months) than with tamoxifen (5.8 months; 95% CI, 5.3 to 8.1 months). However, these early differences (Wilcoxon P ϭ .028) did not translate to a longer-term benefit in PFS, the primary study end point (log-rank P ϭ .121). There was also no difference in survival between both study arms. ConclusionExemestane is an effective and well-tolerated first-line hormonal treatment for postmenopausal women with MBC and offers significant early improvement in time to tumor progression when compared with tamoxifen.

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Localised osteosarcoma will be cured in 50% of patients with cisplatin and doxorubicin. Large randomised trials can be conducted in this rare cancer. Failure to improve survival over 20 years argues for concerted collaborative international efforts to identify and rapidly test new treatments.