Division of Clinical Research, Instituto Nacional de Câncer (INCA), Rio de Janeiro (RJ), Brazil.
Department of Abdomino-Pelvic Surgery, Instituto Nacional de Câncer (INCA), Rio de Janeiro (RJ), Brazil.
Clin Colorectal Cancer. 2022 Sep;21(3):e196-e204. doi: 10.1016/j.clcc.2022.05.002. Epub 2022 May 13.
INDUCTION: chemotherapy (IC) followed by chemoradiation (CRT) is an attractive approach in high-risk locally advanced rectal cancer. Additionally, ASA has shown potential to improve outcomes alongside CRT in rectal cancer. The ICAR trial aimed to evaluate the safety and efficacy of IC followed by CRT with or without ASA on MRI tumor response.
Single-center, double-blind, randomized phase II trial to evaluate induction treatment with CAPOX, followed by capecitabine-based chemoradiotherapy with ASA (arm 1) or placebo (arm 2) in high-risk stage II-III rectal adenocarcinoma staged by MRI. The primary endpoint was MRI tumor regression grade (mrTRG). Secondary endpoints were pathological response, surgical outcomes, postoperative complications, treatment tolerance, DFS, and OS.
Between January 2018 and August 2019, 27 patients were eligible, 25 (92.5%) completed IC, and 23 patients were randomly assigned (12 to ASA group; 11 to placebo group). In the ASA arm, 3 pts (25%) presented distant disease progression at restaging. Seven patients (30.4%) had cCR after neoadjuvant treatment. All 13 patients submitted to surgery after neoadjuvant treatment underwent R0 resections except for 1 patient with positive CRM, and 12 patients (92.3%) had sphincter preservation. After a median follow-up of 34.9 months, the 2-year DFS was 83.1% and 3-year OS was 81.5%.
There was good compliance in both treatment arms and encouraging cCR rate. ASA during CRT was safe but failed to improve on MRI tumor response. The study was closed due to the absence of benefits.
诱导治疗：化疗（IC）后行放化疗（CRT）是高危局部进展期直肠癌的一种有吸引力的方法。此外，ASA 已显示出与 CRT 联合应用于直肠癌时改善疗效的潜力。ICAR 试验旨在评估 IC 后 CRT 联合或不联合 ASA 在 MRI 肿瘤反应方面的安全性和有效性。
单中心、双盲、随机Ⅱ期试验，评估 CAPOX 诱导治疗后，高风险Ⅱ-Ⅲ期直肠腺癌患者接受基于卡培他滨的 CRT 联合 ASA（A 组）或安慰剂（B 组）治疗。主要终点为 MRI 肿瘤消退分级（mrTRG）。次要终点为病理反应、手术结果、术后并发症、治疗耐受性、DFS 和 OS。
2018 年 1 月至 2019 年 8 月，共有 27 例患者符合条件，25 例（92.5%）完成 IC，23 例患者被随机分配（ASA 组 12 例，安慰剂组 11 例）。在 ASA 组，3 例（25%）患者在重新分期时出现远处疾病进展。新辅助治疗后，7 例（30.4%）患者达到 cCR。新辅助治疗后接受手术的 13 例患者均行 R0 切除术，除 1 例 CRM 阳性外，12 例（92.3%）患者保留了肛门括约肌。中位随访 34.9 个月后，2 年 DFS 为 83.1%，3 年 OS 为 81.5%。
两组患者的依从性均较好，且 cCR 率较高。CRT 期间使用 ASA 是安全的，但未能改善 MRI 肿瘤反应。由于缺乏获益，该研究提前关闭。
