编译：南南和北北
来源：桓兴医讯
目的
在早期乳腺癌中评价小剂量口服环磷酰胺和甲氨蝶呤维持治疗，既往证明，这种维持治疗在晚期乳腺癌中有抗肿瘤效果、副作用少。
To evaluate the benefit of low-dose cyclophosphamide and methotrexate (CM) maintenance, which previously demonstrated antitumor activity and few adverse effects in advanced breast cancer, in early breast cancer.
患者和方法
“国际乳腺癌研究组（IBCSG）”22-00试验是一随机III期临床试验，自2000年11月至2012年12月入组了1086名（意向治疗分析1081名）妇女。激素受体阴性、雌激素受体阴性（免疫组化检查阳性细胞<10%）早期乳腺癌妇女，且不论淋巴结和人表皮生长因子受体2（HER2）状态如何，在初次手术到辅助化疗最后一个周期首日后56天内，这段时间窗的任何时间进行随机分组，分组到小剂量口服环磷酰胺和甲氨蝶呤维持治疗组（持续口服环磷酰胺50mg/天，每周第1、2天口服甲氨蝶呤2.5mg，两次/天，用药1年），或非维持治疗组。主要终点为无病生存率，无病生存包括无浸润性复发、无第二恶性肿瘤（乳腺和非乳腺）、无死亡。
International Breast Cancer Study Group (IBCSG) Trial 22-00, a randomized phase III clinical trial, enrolled 1,086 women (1,081 intent-to-treat) from November 2000 to December 2012. Women with estrogen receptor– and progesterone receptor–negative (< 10% positive cells by immunohistochemistry) early breast cancer any nodal and human epidermal growth factor receptor 2 status, were randomly assigned anytime between primary surgery and 56 days after the first day of last course of adjuvant chemotherapy to CM maintenance (cyclophosphamide 50 mg/day orally continuously and methotrexate 2.5 mg twice/day orally on days 1 and 2 of every week for 1 year) or to no CM. The primary end point was disease-free survival (DFS), which included invasive recurrences, second (breast and nonbreast) malignancies, and deaths.
结果
随访6.9年后，分配到环磷酰胺和甲氨蝶呤维持治疗组的患者，相较于分组到无维持治疗组者，总的无病生存率（风险比[HR]0.84，95%CI0.66-1.06，P=0.14）和三阴乳腺癌者无病生存率（n=814名，HR0.80，95%CI0.60-1.06）,均没有明显更好。淋巴结阳性的三阴乳腺癌患者风险比有下降，但没有统计学意义（n=340，HR0.72，95%CI0.49-1.05）。分配到维持治疗组的542名患者中有71名（13%）没有进行维持治疗。接受过至少一个维持治疗剂量的473名患者（包括2名分组到非维持组）中，64名（14%）经历了3或4级治疗相关的不良反应，转氨酶升高是最常见的不良反应(7%)，其次为白细胞减少症（2%）。
After a median of 6.9 years of follow-up, DFS was not significantly better for patients assigned to CM maintenance compared with patients assigned to no CM, both overall (hazard ratio [HR], 0.84; 95% CI, 0.66 to 1.06;P = .14) and in triple-negative (TN) disease (n = 814; HR, 0.80; 95% CI, 0.60 to 1.06). Patients with TN, node-positive disease had a nonstatistically significant reduced HR (n = 340; HR, 0.72; 95% CI, 0.49 to 1.05). Seventy-one (13%) of 542 patients assigned to CM maintenance did not start CM. Of 473 patients who received at least one CM maintenance dose (including two patients assigned to no CM), 64 (14%) experienced a grade 3 or 4 treatment-related adverse event; elevated serum transaminases was the most frequently reported (7%), followed by leukopenia (2%).
结论
在激素受体阴性早期乳腺癌中，环磷酰胺和甲氨蝶呤维持治疗未显著降低无病生存率。在淋巴结阳性的三阴乳腺癌亚组中所观察到的获益趋势，值得在更高危的三阴乳腺癌患者中进一步探索这种治疗策略。
CM maintenance did not produce a significant reduction in DFS events in hormone receptor–negative early breast cancer. The trend toward benefit observed in the TN, node-positive subgroup supports additional exploration of this strategy in the TN, higher-risk population.
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