新辅助改良 FOLFOX6 联合或不联合放疗对比氟尿嘧啶联合放疗治疗局部进展期直肠癌：中国 FOWARC 试验的最终结果。

Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial.

机构信息

The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Guangzhou, People's Republic of China.

Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.

出版信息

J Clin Oncol. 2019 Dec 1;37(34):3223-3233. doi: 10.1200/JCO.18.02309. Epub 2019 Sep 26.

PURPOSE

In the multicenter, open-label, phase III FOWARC trial, modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus radiotherapy resulted in a higher pathologic complete response rate than fluorouracil plus radiotherapy in Chinese patients with locally advanced rectal cancer. Here, we report the final results.

METHODS

Adults ages 18 to 75 years with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil (leucovorin 400 mg/m, fluorouracil 400 mg/m, and fluorouracil 2.4 g/m over 48 hours) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 to 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS).

RESULTS

In total, 495 patients were randomly assigned to treatment. After a median follow-up of 45.2 months, DFS events were reported in 46, 39, and 46 patients in the fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, and mFOLFOX6 arms. In each arm, the probability of 3-year DFS was 72.9%, 77.2%, and 73.5% ( = .709 by the log-rank test), the 3-year probability of local recurrence after R0/1 resection was 8.0%, 7.0%, and 8.3% ( = .873 by the log-rank test), and the 3-year overall survival rate was 91.3%, 89.1%, and 90.7% ( = .971 by log-rank test), respectively.

CONCLUSION

mFOLFOX6, with or without radiation, did not significantly improve 3-year DFS versus fluorouracil with radiation in patients with locally advanced rectal cancer. No significant difference in outcomes was found between mFOLFOX6 without radiotherapy and fluorouracil with radiotherapy, which requires additional investigation of the role of radiotherapy in these regimens.

目的

在多中心、开放标签、III 期 FOWARC 试验中，改良的持续输注氟尿嘧啶、亚叶酸钙和奥沙利铂（mFOLFOX6）联合放疗在局部晚期直肠癌中国患者中的病理完全缓解率高于氟尿嘧啶联合放疗。在此，我们报告最终结果。

方法

年龄在 18 至 75 岁之间、II/III 期直肠癌患者被随机分为三组（1:1:1），分别接受五周期持续输注氟尿嘧啶（亚叶酸钙 400mg/m2，氟尿嘧啶 400mg/m2，氟尿嘧啶 2400mg/m2，持续 48 小时）联合放疗（周期 2 至 4 期间，分 23 至 25 次给予 46.0 至 50.4Gy），随后进行手术，以及七周期持续输注氟尿嘧啶，同一治疗方案加上每个周期第一天静脉注射奥沙利铂 85mg/m2（mFOLFOX6），或四至六周期 mFOLFOX6 联合放疗，随后进行六至八周期 mFOLFOX6。主要终点是 3 年无病生存率（DFS）。

结果

共 495 例患者被随机分配至治疗组。中位随访 45.2 个月后，氟尿嘧啶联合放疗、mFOLFOX6 联合放疗和 mFOLFOX6 组分别有 46、39 和 46 例患者出现疾病进展。在每个治疗组中，3 年 DFS 的概率分别为 72.9%、77.2%和 73.5%（对数秩检验， =.709），R0/1 切除后 3 年局部复发率分别为 8.0%、7.0%和 8.3%（对数秩检验， =.873），3 年总生存率分别为 91.3%、89.1%和 90.7%（对数秩检验， =.971）。