A RANDOMIZED CLINICAL-TRIAL EVALUATING SEQUENTIAL METHOTREXATE AND FLUOROURACIL IN THE TREATMENT OF PATIENTS WITH NODE-NEGATIVE BREAST-CANCER WHO HAVE ESTROGEN-RECEPTOR-NEGATIVE TUMORS
A RANDOMIZED CLINICAL-TRIAL EVALUATING SEQUENTIAL METHOTREXATE AND FLUOROURACIL IN THE TREATMENT OF PATIENTS WITH NODE-NEGATIVE BREAST-CANCER WHO HAVE ESTROGEN-RECEPTOR-NEGATIVE TUMORS
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DOI：
10.1056/nejm198902233200801
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发表时间：
1989-02-23
影响因子：
158.5
通讯作者：
CAPLAN, R
中科院分区：
文献类型：
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作者：
FISHER, B;REDMOND, C;CAPLAN, R
我们评估了679例原发性乳腺癌、组织学阴性腋窝淋巴结和雌激素受体阴性（< 10 fmol）肿瘤患者术后序贯使用甲氨蝶呤和氟尿嘧啶，随后使用亚叶酸的情况。在4年的随访中，与无术后治疗相比，未观察到该治疗的生存优势（87% vs. 86%; P=0.8）。然而，接受这种治疗的妇女与未接受这种治疗的妇女相比，无病生存期显著延长（80%对71%; P=0.003）。在两个患者中观察到优势。49岁和那些. gtoreq. 50.四年后，年轻组的治疗失败率降低了24%，老年组降低了50%。局部、区域和远处转移率均降低。这些益处在不使用烷基化剂的情况下实现，与可耐受的副作用相关。潜在相互作用的多变量分析测试未能识别未从治疗中获益的患者亚组。这些结果虽然有希望，但并不意味着需要进行额外的试验来评估潜在的更好的治疗方案，但它们确实表明，在此类研究中，应在对照组中使用序贯甲氨蝶呤-氟尿嘧啶。如果患者符合本研究的合格标准，则其用于治疗拒绝参加临床试验的患者也是合理的。由于肿瘤太小，无法进行雌激素受体和孕酮受体浓度常规分析的女性未纳入本研究，因此我们不建议在临床试验之外对其进行全身治疗。
We evaluated the postoperative use of sequential methotrexate and fluorouracil followed by leucovorin in 679 patients with primary breast cancer, histologically negative axillary nodes, and estrogen-receptor-negative (< 10 fmol) tumors. No survival advantage was observed with this therapy as compared with no postoperative therapy during four years of follow-up (87 percent vs. 86 percent; P=0.8). However, there was a significant prolongation of disease-free survival among women who received this therapy as compared with those who did not (80 percent vs. 71 percent; P=0.003). An advantage was observed in both the patients .ltoreq. 49 years old and those .gtoreq. 50. At four years, treatment failure was reduced by 24 percent in the younger group and by 50 percent in the older group. The rates of both local and regional and distant metastases were decreased. These benefits, achieved without the use of an alkylating agent, were associated with tolerable side effects. Multivariate analysis testing for potential interactions failed to identify subgroups of patients who did not benefits from the therapy. These results, although promising, do not obviate the need for additional trials to evaluate potentially better regimens of therapy, but they do suggest that sequential methotrexate-fluorouracil should be used in the control arm in such studies. Their use is also justified for the treatment of patients who refuse to participate in clinical trials, provided the patients meet the eligibility criteria of the present study. Since women with tumors too small for conventional analysis of estrogen-receptor and progesterone-receptor concentrations were not included in this study, we do not recommend systemic treatment for them outside of a clinical trial.