Rouëssé Jacques, de la Lande Brigitte, Bertheault-Cvitkovic Frédérique, Serin Daniel, Graïc Yvon, Combe Martin, Leduc Bernard, Lucas Virginie, Demange Liliane, Nguyen Tan Dat, Castèra Daniel, Krzisch Claude, Villet Richard, Mouret-Fourme Emmanuelle, Garbay Jean-Rémy, Noguès Catherine
Centre René Huguenin, Saint-Cloud, France.
Int J Radiat Oncol Biol Phys. 2006 Mar 15;64(4):1072-80. doi: 10.1016/j.ijrobp.2005.10.011.
To compare concomitant and sequential adjuvant chemoradiotherapy regimens in node-positive, operable breast cancer patients.
This was a randomized, French, multicenter, phase III trial enrolling 638 eligible women with prior breast surgery and positive axillary dissection. Patients in Arm A received 500 mg/m2 5-fluorouracil, 12 mg/m2 mitoxantrone, and 500 mg/m2 cyclophosphamide, with concomitant radiotherapy (50 Gy +/- 10-20-Gy boost). Patients in Arm B received 500 mg/m2 5-fluorouracil, 60 mg/m2 epirubicin, and 500 mg/m2 cyclophosphamide, with subsequent radiotherapy. Chemotherapy was administered on Day 1 every 21 days for 4 cycles.
Median treatment durations were 64 and 126 days (Arms A and B, respectively), with no significant difference in overall or disease-free survival. Five-year locoregional relapse-free survival favored patients with conservative surgery (two thirds of the population), with less local and/or regional recurrence in Arm A than in Arm B (3% vs. 9%; p = 0.01). Multivariate analysis in this subgroup showed a 2.8-fold increased risk of locoregional recurrence with sequential chemoradiotherapy, independent of other prognostic factors (p = 0.027). Febrile neutropenia and Grade 3-4 leukopenia were significantly more frequent in Arm A. Subclinical left ventricular ejection fraction events at 1 year were more frequent with concomitant radiotherapy (p = 0.02).
Concomitant radiotherapy with adjuvant fluorouracil, mitoxantrone, and cyclophosphamide has significantly better locoregional control in node-positive breast cancer after conservative surgery and 50% shorter treatment, albeit with slightly more acute toxicity. With mitoxantrone no longer available for adjuvant breast cancer treatment, alternative concomitant chemoradiotherapy studies are needed.
比较在腋窝淋巴结阳性、可手术乳腺癌患者中同步和序贯辅助放化疗方案。
这是一项法国多中心随机III期试验，纳入638例先前接受过乳腺癌手术且腋窝淋巴结清扫阳性的合格女性。A组患者接受500mg/m²氟尿嘧啶、12mg/m²米托蒽醌和500mg/m²环磷酰胺，并同步放疗（50Gy±10 - 20Gy加量）。B组患者接受500mg/m²氟尿嘧啶、60mg/m²表柔比星和500mg/m²环磷酰胺，随后进行放疗。化疗每21天在第1天给药，共4个周期。
中位治疗持续时间分别为64天和126天（A组和B组），总生存或无病生存无显著差异。五年局部区域无复发生存率有利于接受保乳手术的患者（占总人群的三分之二），A组局部和/或区域复发少于B组（3%对9%；p = 0.01）。该亚组的多因素分析显示，序贯放化疗的局部区域复发风险增加2.8倍，独立于其他预后因素（p = 0.027）。A组发热性中性粒细胞减少和3 - 4级白细胞减少明显更常见。同步放疗1年时亚临床左心室射血分数事件更常见（p = 0.02）。
在保乳手术后，同步放疗联合辅助氟尿嘧啶、米托蒽醌和环磷酰胺在腋窝淋巴结阳性乳腺癌中具有显著更好的局部区域控制，且治疗时间缩短50%，尽管急性毒性略高。由于米托蒽醌不再用于辅助性乳腺癌治疗，需要开展替代的同步放化疗研究。
