早期乳腺癌的长程治疗、医源性闭经与生存
Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer.
机构信息
National Surgical Adjuvant Breast and Bowel Project, Washington Cancer Institute at Washington Hospital Center, Washington, DC 20010, USA.
出版信息
N Engl J Med. 2010 Jun 3;362(22):2053-65. doi: 10.1056/NEJMoa0909638.
BACKGROUND
Chemotherapy regimens that combine anthracyclines and taxanes result in improved disease-free and overall survival among women with operable lymph-node-positive breast cancer. The effectiveness of concurrent versus sequential regimens is not known.
METHODS
We randomly assigned 5351 patients with operable, node-positive, early-stage breast cancer to receive four cycles of doxorubicin and cyclophosphamide followed by four cycles of docetaxel (sequential ACT); four cycles of doxorubicin and docetaxel (doxorubicin-docetaxel); or four cycles of doxorubicin, cyclophosphamide, and docetaxel (concurrent ACT). The primary aims were to examine whether concurrent ACT was more effective than sequential ACT and whether the doxorubicin-docetaxel regimen would be as effective as the concurrent-ACT regimen. The secondary aims were to assess toxic effects and to correlate amenorrhea with outcomes in premenopausal women.
RESULTS
At a median follow-up of 73 months, overall survival was improved in the sequential-ACT group (8-year overall survival, 83%) as compared with the doxorubicin-docetaxel group (overall survival, 79%; hazard ratio for death, 0.83; P=0.03) and the concurrent-ACT group (overall survival, 79%; hazard ratio, 0.86; P=0.09). Disease-free survival was improved in the sequential-ACT group (8-year disease-free survival, 74%) as compared with the doxorubicin-docetaxel group (disease-free survival, 69%; hazard ratio for recurrence, a second malignant condition, or death, 0.80; P=0.001) and the concurrent-ACT group (disease-free survival, 69%; hazard ratio, 0.83; P=0.01). The doxorubicin-docetaxel regimen showed noninferiority to the concurrent-ACT regimen for overall survival (hazard ratio, 0.96; 95% confidence interval, 0.82 to 1.14). Overall survival was improved in patients with amenorrhea for 6 months or more across all treatment groups, independently of estrogen-receptor status.
CONCLUSIONS
Sequential ACT improved disease-free survival as compared with doxorubicin-docetaxel or concurrent ACT, and it improved overall survival as compared with doxorubicin-docetaxel. Amenorrhea was associated with improved survival regardless of the treatment and estrogen-receptor status. (ClinicalTrials.gov number, NCT00003782.)
背景
在患有可手术的淋巴结阳性乳腺癌的女性中，联合应用蒽环类药物和紫杉烷类药物的化疗方案可改善无病生存和总生存。同期与序贯方案的有效性尚不清楚。
方法
我们将 5351 例可手术、淋巴结阳性、早期乳腺癌患者随机分为四组：接受多柔比星和环磷酰胺 4 个周期，然后是多西紫杉醇 4 个周期（序贯 ACT）；多柔比星和多西紫杉醇 4 个周期（多柔比星-多西紫杉醇）；或多柔比星、环磷酰胺和多西紫杉醇 4 个周期（同期 ACT）。主要目的是检验同期 ACT 是否优于序贯 ACT，以及多柔比星-多西紫杉醇方案是否与同期 ACT 方案同样有效。次要目的是评估毒副作用，并将绝经前妇女的闭经与结局相关联。
结果
中位随访 73 个月时，与多柔比星-多西紫杉醇组（总生存 79%；死亡风险比，0.83；P=0.03）和同期 ACT 组（总生存 79%；死亡风险比，0.86；P=0.09）相比，序贯 ACT 组的总生存得到改善（8 年总生存率 83%）。与多柔比星-多西紫杉醇组（无病生存率 69%；复发、第二恶性肿瘤或死亡风险比，0.80；P=0.001）和同期 ACT 组（无病生存率 69%；复发、第二恶性肿瘤或死亡风险比，0.83；P=0.01）相比，序贯 ACT 组的无病生存率得到改善（8 年无病生存率 74%）。多柔比星-多西紫杉醇方案在总生存方面不劣于同期 ACT 方案（风险比，0.96；95%置信区间，0.82 至 1.14）。所有治疗组中，闭经 6 个月或以上的患者的总生存均得到改善，与雌激素受体状态无关。
结论
与多柔比星-多西紫杉醇或同期 ACT 相比，序贯 ACT 可改善无病生存，与多柔比星-多西紫杉醇相比，序贯 ACT 可改善总生存。无论治疗和雌激素受体状态如何，闭经与生存改善相关。（临床试验.gov 编号，NCT00003782。）
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