一项比较局部进展期直肠癌术前放化疗后巩固化疗与单纯放化疗的随机 2 期临床试验：KCSG CO 14-03。
A Randomized Phase 2 Trial of Consolidation Chemotherapy After Preoperative Chemoradiation Therapy Versus Chemoradiation Therapy Alone for Locally Advanced Rectal Cancer: KCSG CO 14-03.
机构信息
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Biometric Research Branch, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
出版信息
Int J Radiat Oncol Biol Phys. 2018 Jul 15;101(4):889-899. doi: 10.1016/j.ijrobp.2018.04.013. Epub 2018 Apr 12.
PURPOSE
Preoperative chemoradiation therapy (CRT) followed by total mesorectal excision (TME) in locally advanced rectal cancer is the standard of care. To date, the role of consolidation chemotherapy after CRT has rarely been addressed through randomized trials. This study aimed to evaluate the efficacy of CRT followed by consolidation chemotherapy compared with CRT alone.
METHODS AND MATERIALS
This study enrolled patients with adenocarcinoma of the rectum and cT3 or cT4 disease with any N category and no metastasis. In arm A (control arm), we planned CRT (50.4 Gy in 28 fractions) with capecitabine followed by TME. In arm B, 2 cycles of capecitabine and oxaliplatin were administered 1 week after the completion of CRT before TME (capecitabine, 1700 mg/m per day from day 1 to 14, and oxaliplatin, 100 mg/m on day 1, every 3 weeks). The downstaging rate (the proportion of ypT0 to ypT2 and ypN0M0) was the primary endpoint, which was to be tested with a 1-sided type I error of 15% and with 85% power.
RESULTS
From September 2014 to February 2016, 110 patients (56 in arm A and 54 in arm B) were randomized and 108 (55 in arm A and 53 in arm B) started CRT. TME was conducted per protocol in 96 patients (52 in arm A and 44 in arm B). In arms A and B, downstaging was achieved in 21.2% and 36.4% (P = .077), respectively, and the pathologic complete response rate was 5.8% and 13.6% (P = .167), respectively. Grade ≥3 adverse events occurred in 3.6% of patients in arm A and 9.4% of patients in arm B during the preoperative treatment phase and in 1.9% and 9.0%, respectively, during the postoperative recovery phase.
CONCLUSIONS
Consolidation chemotherapy with 2 cycles of capecitabine and oxaliplatin demonstrated a marginal improvement in the downstaging rate. However, a phase 3 trial of this strategy is discouraged because of the high dropout rate and safety issues.
目的
局部晚期直肠癌的术前放化疗（CRT）加全直肠系膜切除术（TME）是标准治疗方法。迄今为止，通过随机试验很少探讨 CRT 后巩固化疗的作用。本研究旨在评估 CRT 加巩固化疗与 CRT 单独治疗相比的疗效。
方法和材料
这项研究纳入了直肠腺癌患者，cT3 或 cT4 疾病，任何 N 分期和无转移。在 A 臂（对照组）中，我们计划进行 CRT（50.4Gy，28 个分次），并用卡培他滨治疗，然后进行 TME。在 B 臂中，在 CRT 完成后 1 周内给予 2 个周期的卡培他滨和奥沙利铂，然后再进行 TME（卡培他滨，第 1 天至第 14 天每天 1700mg/m2，奥沙利铂，第 1 天 100mg/m2，每 3 周 1 次）。降期率（ypT0 至 ypT2 和 ypN0M0 的比例）是主要终点，用单侧 α 错误为 15%和 85%功效进行检验。
结果
从 2014 年 9 月至 2016 年 2 月，110 例患者（A 臂 56 例，B 臂 54 例）被随机分组，108 例（A 臂 55 例，B 臂 53 例）开始接受 CRT。96 例患者按方案进行 TME（A 臂 52 例，B 臂 44 例）。A 臂和 B 臂的降期率分别为 21.2%和 36.4%（P=.077），病理完全缓解率分别为 5.8%和 13.6%（P=.167）。术前治疗阶段，A 臂和 B 臂分别有 3.6%和 9.4%的患者发生≥3 级不良事件，术后恢复阶段分别有 1.9%和 9.0%的患者发生≥3 级不良事件。
结论
2 个周期的卡培他滨和奥沙利铂巩固化疗显示出降期率的轻微改善。然而，由于高脱落率和安全性问题，不鼓励进行该策略的 3 期试验。
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