Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
J Clin Oncol. 2011 Jul 10;29(20):2773-80. doi: 10.1200/JCO.2010.34.4911. Epub 2011 May 23.
To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer.
Seven hundred forty-seven patients with resectable, locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the mid-low rectum were randomly assigned to receive pelvic radiation (50.4 Gy in 28 daily fractions) and concomitant infused fluorouracil (225 mg/m(2)/d) either alone (arm A, n = 379) or combined with oxaliplatin (60 mg/m(2) weekly × 6; arm B, n = 368). Overall survival is the primary end point. A protocol-planned analysis of response to preoperative treatment is reported here.
Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone (24% v 8% of treated patients; P < .001). In arm B, 83% of the patients treated with oxaliplatin had five or more weekly administrations. Ninety-one percent, compared with 97% in the control arm, received ≥ 45 Gy (P < .001). Ninety-six percent versus 95% of patients underwent surgery with similar rates of abdominoperineal resections (20% v 18%, arm A v arm B). The rate of pathologic complete responses was 16% in both arms (odds ratio = 0.98; 95% CI, 0.66 to 1.44; P = .904). Twenty-six percent versus 29% of patients had pathologically positive lymph nodes (arm A v arm B; P = .447), 46% versus 44% had tumor infiltration beyond the muscularis propria (P = .701), and 7% versus 4% had positive circumferential resection margins (P = .239). Intra-abdominal metastases were found at surgery in 2.9% versus 0.5% of patients (arm A v arm B; P = .014).
Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy significantly increases toxicity without affecting primary tumor response. Longer follow-up is needed to assess the impact on efficacy end points.
研究奥沙利铂联合氟尿嘧啶为基础的放化疗作为局部晚期直肠癌的术前治疗。
747 例可切除的局部晚期（cT3-4 和/或 cN1-2）中低位直肠腺癌患者随机分为两组，接受盆腔放疗（28 个每日分割剂量 50.4 Gy）和同时输注氟尿嘧啶（225mg/m2/d），单纯接受放疗（A 组，n=379）或联合奥沙利铂（每周 6 次 60mg/m2；B 组，n=368）。总生存是主要终点。本研究报告了术前治疗反应的方案计划分析。
奥沙利铂联合氟尿嘧啶和放疗的 3-4 级不良反应发生率明显高于单纯放疗和氟尿嘧啶（治疗患者的 24%比 8%；P<.001）。在 B 组，83%接受奥沙利铂治疗的患者每周接受 5 次或以上治疗。91%的患者接受了≥45Gy（与对照组相比，P<.001）。96%与 95%的患者接受了手术，且腹会阴切除术的比例相似（20%比 18%，A 组比 B 组）。两组的病理完全缓解率均为 16%（优势比=0.98；95%置信区间，0.66 至 1.44；P=0.904）。两组的病理阳性淋巴结率分别为 26%和 29%（A 组比 B 组；P=0.447），肌层外肿瘤浸润率分别为 46%和 44%（P=0.701），切缘阳性率分别为 7%和 4%（P=0.239）。术中发现腹腔转移分别为 2.9%和 0.5%（A 组比 B 组；P=0.014）。
在氟尿嘧啶为基础的术前放化疗中加入奥沙利铂显著增加了毒性，而不影响原发肿瘤的反应。需要更长的随访时间来评估对疗效终点的影响。
