老年早期乳腺癌女性的辅助化疗
Adjuvant chemotherapy in older women with early-stage breast cancer.
作者信息
Muss Hyman B, Berry Donald A, Cirrincione Constance T, Theodoulou Maria, Mauer Ann M, Kornblith Alice B, Partridge Ann H, Dressler Lynn G, Cohen Harvey J, Becker Heather P, Kartcheske Patricia A, Wheeler Judith D, Perez Edith A, Wolff Antonio C, Gralow Julie R, Burstein Harold J, Mahmood Ahmad A, Magrinat Gustav, Parker Barbara A, Hart Ronald D, Grenier Debjani, Norton Larry, Hudis Clifford A, Winer Eric P
机构信息
University of Vermont, Burlington, USA.
出版信息
N Engl J Med. 2009 May 14;360(20):2055-65. doi: 10.1056/NEJMoa0810266.
BACKGROUND
Older women with breast cancer are underrepresented in clinical trials, and data on the effects of adjuvant chemotherapy in such patients are scant. We tested for the noninferiority of capecitabine as compared with standard chemotherapy in women with breast cancer who were 65 years of age or older.
METHODS
We randomly assigned patients with stage I, II, IIIA, or IIIB breast cancer to standard chemotherapy (either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide plus doxorubicin) or capecitabine. Endocrine therapy was recommended after chemotherapy in patients with hormone-receptor-positive tumors. A Bayesian statistical design was used with a range in sample size from 600 to 1800 patients. The primary end point was relapse-free survival.
RESULTS
When the 600th patient was enrolled, the probability that, with longer follow-up, capecitabine therapy was highly likely to be inferior to standard chemotherapy met a prescribed level, and enrollment was discontinued. After an additional year of follow-up, the hazard ratio for disease recurrence or death in the capecitabine group was 2.09 (95% confidence interval, 1.38 to 3.17; P<0.001). Patients who were randomly assigned to capecitabine were twice as likely to have a relapse and almost twice as likely to die as patients who were randomly assigned to standard chemotherapy (P=0.02). At 3 years, the rate of relapse-free survival was 68% in the capecitabine group versus 85% in the standard-chemotherapy group, and the overall survival rate was 86% versus 91%. Two patients in the capecitabine group died of treatment-related complications; as compared with patients receiving capecitabine, twice as many patients receiving standard chemotherapy had moderate-to-severe toxic effects (64% vs. 33%).
CONCLUSIONS
Standard adjuvant chemotherapy is superior to capecitabine in patients with early-stage breast cancer who are 65 years of age or older. (ClinicalTrials.gov number, NCT00024102.)
背景
老年乳腺癌女性在临床试验中的代表性不足，关于此类患者辅助化疗效果的数据也很匮乏。我们对卡培他滨与标准化疗在65岁及以上乳腺癌女性中的非劣效性进行了测试。
方法
我们将I期、II期、IIIA期或IIIB期乳腺癌患者随机分配至标准化疗组（环磷酰胺、甲氨蝶呤和氟尿嘧啶或环磷酰胺加阿霉素）或卡培他滨组。激素受体阳性肿瘤患者在化疗后推荐接受内分泌治疗。采用贝叶斯统计设计，样本量范围为600至1800例患者。主要终点为无复发生存期。
结果
当纳入第600例患者时，随着随访时间延长，卡培他滨治疗极有可能劣于标准化疗的概率达到了规定水平，于是停止入组。在额外随访一年后，卡培他滨组疾病复发或死亡的风险比为2.09（95%置信区间为1.38至3.17；P<0.001）。随机分配至卡培他滨组的患者复发可能性是随机分配至标准化疗组患者的两倍，死亡可能性几乎也是两倍（P=0.02）。3年时，卡培他滨组无复发生存率为68%，标准化疗组为85%；总生存率分别为86%和91%。卡培他滨组有2例患者死于治疗相关并发症；与接受卡培他滨治疗的患者相比，接受标准化疗的患者发生中度至重度毒性反应的人数是其两倍（64%对33%）。
结论
对于65岁及以上的早期乳腺癌患者，标准辅助化疗优于卡培他滨。（临床试验注册号：NCT00024102。）
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