Cheng Yu, Wu Gang, Zhang Simeng, Liu Yunpeng, Qu Jinglei, Qu Xiujuan
Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, People's Republic of China.
Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, People's Republic of China.
Onco Targets Ther. 2021 Jul 15;14:4201-4209. doi: 10.2147/OTT.S320477. eCollection 2021.
Doublet or triplet chemotherapy plus or minus targeted drugs can achieve a high objective response rate (ORR) and are currently considered to be the backbone of conventional therapy for liver metastatic colorectal cancer (mCRC). However, current biomarkers (such as UGT1A1 and DPYD) are limited to the prediction of toxicity and there are no effective biomarkers to predict chemotherapy response. Therefore, personalized cancer chemotherapy underpinned by genomic alterations in mCRC has received increasing attention.
We present a case of a 28-year-old female rectal cancer patient with multiple liver metastases (clinical risk score, CRS = 5 points). The patient underwent XELOXIRI plus bevacizumab regimen that consisted of irinotecan (150 mg/m2), oxaliplatin (100 mg/m2) on day 1, capecitabine (1700 mg/m2 per day from day 2 to 15), bevacizumab (7.5 mg/kg) on day 1 (on the second cycle), given every three weeks for eight cycles. After multi-disciplinary team (MDT) discussion, the patient underwent right hemihepatectomy, partial liver resection of segment IV and cholecystectomy. Surprisingly, the patient achieved a complete pathologic response (pCR) of the hepatic metastasis and clinical complete response (cCR) of the primary rectal lesion. A paired tumor molecular profile revealed somatic mutations in ataxia-telangiectasia mutated (ATM) genes that may explain why the patient achieved such a dramatic tumor response. Treatment was discontinued after eight cycles of a single oral dose of capecitabine and the patient started a follow-up program of physical and radiological examinations. To monitor the signs of recurrence, we also obtained blood samples to analyze circulating tumor DNA (ctDNA). To date, the patient has remained disease-free.
The XELOXIRI-bevacizumab regimen is a feasible and effective regimen for patients with mCRC. Mutations in the ATM genes may characterize a subset of patients with a better prognosis who are more sensitive to chemotherapy plus biological agents.
双联或三联化疗联合或不联合靶向药物可实现较高的客观缓解率(ORR),目前被认为是肝转移结直肠癌(mCRC)传统治疗的基础。然而,目前的生物标志物(如UGT1A1和DPYD)仅限于预测毒性,尚无有效的生物标志物来预测化疗反应。因此,基于mCRC基因组改变的个性化癌症化疗受到了越来越多的关注。
我们报告一例28岁女性直肠癌患者,伴有多发肝转移(临床风险评分,CRS = 5分)。患者接受了XELOXIRI联合贝伐单抗方案,该方案包括伊立替康(150 mg/m²)、第1天的奥沙利铂(100 mg/m²)、第2至15天的卡培他滨(1700 mg/m²/天)、第1天(第二个周期)的贝伐单抗(7.5 mg/kg),每三周给药一次,共八个周期。经过多学科团队(MDT)讨论,患者接受了右半肝切除术、IV段部分肝切除术和胆囊切除术。令人惊讶的是,患者肝转移灶达到了完全病理缓解(pCR),原发直肠病变达到了临床完全缓解(cCR)。配对的肿瘤分子谱显示共济失调毛细血管扩张突变(ATM)基因存在体细胞突变,这可能解释了患者为何能获得如此显著的肿瘤反应。在八个周期的单剂量口服卡培他滨治疗后停止治疗,患者开始了体格检查和影像学检查的随访计划。为了监测复发迹象,我们还采集了血样以分析循环肿瘤DNA(ctDNA)。迄今为止,患者仍无疾病复发。
XELOXIRI-贝伐单抗方案对mCRC患者是一种可行且有效的方案。ATM基因突变可能是对化疗加生物制剂更敏感、预后较好的患者亚群的特征。