von Minckwitz Gunter, Kümmel Sherko, Vogel Petra, Hanusch Claus, Eidtmann Holger, Hilfrich Jörn, Gerber Bernd, Huober Jens, Costa Serban Dan, Jackisch Christian, Loibl Sibylle, Mehta Keyur, Kaufmann Manfred
German Breast Group, Frankfurt, Germany.
J Natl Cancer Inst. 2008 Apr 16;100(8):542-51. doi: 10.1093/jnci/djn085. Epub 2008 Apr 8.
Among breast cancer patients, nonresponse to initial neoadjuvant chemotherapy is associated with unfavorable outcome. We compared the response of nonresponding patients who continued the same treatment with that of patients who switched to a well-tolerated non-cross-resistant regimen.
Previously untreated breast cancer patients received two 3-week cycles of docetaxel at 75 mg/m(2), doxorubicin at 50 mg/m(2), and cyclophosphamide at 500 mg/m(2) per day (TAC). Patients whose tumors did not decrease in size by at least 50% were randomly assigned to four additional cycles of TAC or to four cycles of vinorelbine at 25 mg/m(2) and capecitabine at 2000 mg/m(2) (NX). The outcome was sonographic response, defined as a reduction in the product of the two largest perpendicular diameters by at least 50%. A difference of 10% or less in the sonographic response qualified as noninferiority of the NX treatment. Pathological complete response was defined as no invasive or in situ residual tumor masses in the breast and lymph nodes. Toxic effects were assessed. All statistical tests were two-sided.
Of 2090 patients enrolled in the GeparTrio study, 622 (29.8%) who did not respond to two initial cycles of TAC were randomly assigned to an additional four cycles of TAC (n = 321) or to four cycles of NX (n = 301). Sonographic response rate was 50.5% for the TAC arm and 51.2% for the NX arm. The difference of 0.7% (95% confidence interval = -7.1% to 8.5%) demonstrated noninferiority of NX (P = .008). Similar numbers of patients in both arms received breast-conserving surgery (184 [57.3%] in the TAC arm vs 180 [59.8%] in the NX arm) and had a pathological complete response (5.3% vs 6.0%). Fewer patients in the NX arm than in the TAC arm had hematologic toxic effects, mucositis, infections, and nail changes, but more had hand-foot syndrome and sensory neuropathy.
Pathological complete responses to both regimens were marginal. Among patients who did not respond to the initial neoadjuvant TAC treatment, similar efficacy but better tolerability was observed by switching to NX than continuing with TAC.
在乳腺癌患者中，对初始新辅助化疗无反应与不良预后相关。我们比较了继续相同治疗的无反应患者与改用耐受性良好的非交叉耐药方案的患者的反应情况。
先前未接受过治疗的乳腺癌患者接受两个3周疗程的多西他赛（75mg/m²）、阿霉素（50mg/m²）和环磷酰胺（500mg/m²/天）（TAC）治疗。肿瘤大小未至少缩小50%的患者被随机分配接受另外四个疗程的TAC或四个疗程的长春瑞滨（25mg/m²）和卡培他滨（2000mg/m²）（NX）治疗。结局为超声反应，定义为两个最大垂直直径乘积至少缩小50%。超声反应相差10%或更少被视为NX治疗的非劣效性。病理完全缓解定义为乳腺和淋巴结中无浸润性或原位残留肿瘤肿块。评估毒性作用。所有统计检验均为双侧检验。
在GeparTrio研究纳入的2090例患者中，622例（29.8%）对两个初始疗程的TAC无反应，被随机分配接受另外四个疗程的TAC（n = 321）或四个疗程的NX（n = 301）。TAC组的超声反应率为50.5%，NX组为51.2%。相差0.7%（95%置信区间 = -7.1%至8.5%）表明NX具有非劣效性（P = .008）。两组接受保乳手术的患者数量相似（TAC组1,84例[57.3%]，NX组180例[59.8%]），且病理完全缓解的患者数量相似（5.3%对6.0%）。NX组出现血液学毒性作用、粘膜炎、感染和指甲改变的患者比TAC组少，但出现手足综合征和感觉神经病变的患者更多。
两种方案的病理完全缓解率都很低。在对初始新辅助TAC治疗无反应的患者中，改用NX治疗比继续使用TAC观察到相似的疗效但耐受性更好。
