Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer.
Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer.
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以 UGT1A1 状态为指导的卡培他滨和伊立替康新辅助放化疗治疗局部晚期直肠癌的多中心、随机、III 期试验
DOI：
10.1200/jco.20.01932
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发表时间：
2020-12-20
期刊：
影响因子：
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通讯作者：
Zhang Z
中科院分区：
文献类型：
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作者：
Zhu J;Liu A;Sun X;Liu L;Zhu Y;Zhang T;Jia J;Tan S;Wu J;Wang X;Zhou J;Yang J;Zhang C;Zhang H;Zhao Y;Cai G;Zhang W;Xia F;Wan J;Zhang H;Shen L;Cai S;Zhang Z
根据尿苷二磷酸葡萄糖醛酸转移酶1A 1（UGT 1A 1）基因型区分伊立替康剂量可提高病理完全缓解（pCR）率。在这项研究中，我们进一步研究了术前伊立替康联合卡培他滨为主的放化疗治疗局部晚期直肠癌。患者和方法我们在中国进行了这项随机、开放标签、多中心、III期试验。将符合条件的临床T3-4和/或N+直肠腺癌患者（UGT 1A 1基因型 *1*1或 *1*28）随机分配至对照组：盆腔放疗50戈伊/25次，同时接受卡培他滨，随后接受奥沙利铂和卡培他滨;或实验组：UGT 1A 1 *1*1患者接受卡培他滨联合伊立替康80 mg/m2每周一次放疗，UGT 1A 1 *1*28患者接受伊立替康65 mg/m2每周一次放疗，随后接受伊立替康和卡培他滨。主要终点为pCR。本试验在ClinicalTrials.gov注册（ClinicalTrials.gov标识符：NCT 02605265）。结果在最初入组的360例患者中，356例被评估为改良的意向治疗人群（两组均为178例）。对照组和实验组分别有87%和88%的患者进行了手术。对照组和实验组的pCR率分别为15%（n = 27/178）和30%（n = 53/178）（风险比，1.96; 95%CI，1.30 - 2.97; P = 0.001）。对照组和实验组分别有4例和6例患者达到完全临床缓解。对照组和实验组分别有11例（6%）和68例（38%）患者记录到3-4级毒性（P <0.001）。最常见的3-4级毒性是白细胞减少症、中性粒细胞减少症和腹泻。两组的总体手术并发症发生率无显著差异（11% vs15%; P <0.001）。结论在以卡培他滨为基础的新辅助放化疗中，联合应用UGT 1A 1基因型指导的伊立替康可显著提高中国患者的肿瘤完全缓解率。
PURPOSE Differentiating the irinotecan dose on the basis of the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotype improves the pathologic complete response (pCR) rate. In this study, we further investigated preoperative irinotecan combined with capecitabine-based chemoradiotherapy for locally advanced rectal cancer. PATIENTS AND METHODS We conducted this randomized, open-label, multicenter, phase III trial in China. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma, UGT1A1 genotype *1*1 or *1*28 were randomly allocated to the control group: pelvic radiation of 50 Gy/25 fractions with concurrent capecitabine, followed by oxaliplatin and capecitabine; or the experimental group: radiation with capecitabine combined with weekly irinotecan 80 mg/m2 for patients with UGT1A1*1*1 or 65 mg/m2 for patients with UGT1A1*1*28, followed by irinotecan and capecitabine. The primary end point was pCR. This trial was registered with ClinicalTrials.gov (ClinicalTrials.gov identifier: NCT02605265). RESULTS Of the 360 patients initially enrolled, 356 were evaluated as the modified intention-to-treat population (n = 178 in both groups). Surgery was performed in 87% and 88% of patients in the control and experimental groups, respectively. The pCR rates were 15% (n = 27 of 178) and 30% (n = 53 of 178) in the control and experimental groups (risk ratio, 1.96; 95% CI, 1.30 to 2.97; P = .001). Four and 6 patients achieved complete clinical response in the control and experimental groups, respectively. Grade 3-4 toxicities were recorded in 11 (6%) and 68 (38%) patients in the control and experimental groups, respectively (P < .001). The commonest grade 3-4 toxicities were leukopenia, neutropenia, and diarrhea. The overall surgical complication rate was not significantly different between the two groups (11% v 15%; P < .001). CONCLUSION Adding irinotecan guided by UGT1A1 genotype to capecitabine-based neoadjuvant chemoradiotherapy significantly increased complete tumor response in Chinese patients.
在MRI定义的局部晚期直肠癌中，术前与同时使用的Irinotecan和Capecitabine进行了术前进行化学放疗：I期试验（NWCOG-2）。
影响因子：
8.8
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通讯作者：
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