XELOX方案对比卡培他滨单药方案在老年结直肠癌患者术后辅助化疗中的疗效及安全性探讨

Efficacy and safety of XELOX therapy in comparison with capecitabine monotherapy in adjuvant chemotherapy for elderly patients with colorectal cancer

目的:探讨XELOX方案(卡培他滨联合奥沙利铂)对比卡培他滨单药方案在老年结直肠癌患者术后辅助化疗中的疗效及安全性。方法:本研究纳入从2010年1月到2017年12月在郑州人民医院进行R0手术切除结直肠癌老年患者(60~82岁)195例,术后接受卡培他滨单药或XELOX方案的辅助化疗(根据患者美国东部肿瘤协作组(ECOG)评分、体能状态、医生评估、患者耐受能力及意愿选择辅助化疗方案)。通过医院的病历系统统计入组患者基线临床资料并按照试验方案进行患者随访。两种辅助化疗方案患者的无疾病生存期(DFS)和总生存期(OS)用Kaplan-Meier生存分析方法进行分析。建立Cox风险比例模型,评估在风险因素相同的情况下,两种辅助治疗方案的疗效。依据CTCAE 4.0的标准,记录2级以上不良反应发生情况并进行安全性分析。结果:该研究中位随访5.75年(随访时间范围:0.30~7.50年)。纳入研究的195例患者均可评价疗效,整体患者人群中位无疾病生存期(mDFS)为5.0年,其中XELOX方案组的mDFS为5.5年,显著高于卡培他滨单药方案组的mDFS 3.6年(P=0.047,95%CI:2.06-5.14)。患者整体中位总生存期(mOS)为7.1年,其中XELOX方案组mOS为7.1年,显著高于卡培他滨单药方案组的mOS 4.5年(P=0.021,95%CI:3.30-5.70)。在风险因素相同的情况下,当患者年龄<70岁,无论是DFS(HR=0.74,P=0.036)还是OS(HR=0.78,P=0.041)患者均能够从XELOX方案中获益;当患者年龄≥70岁时,患者仅DFS(HR=0.77,P=0.035)可以从XELOX方案中获益。无论患者合并症状如何,患者的DFS和OS均能从XELOX方案中获益。但是仅当淋巴结送检的枚数≤12枚、患者接受辅助化疗周期数≥6的时候,患者DFS和OS才能从XELOX方案中获益。不良反应方面,中性粒细胞减少(61.54%vs.39.74%,P=0.003)及神经毒性发生率(65.81%vs.0%),XELOX方案组显著高于卡培他滨单药方案组;其他的不良反应,如腹泻、口腔炎、血小板减少、手足综合征、贫血、恶心呕吐、AST/ALT升高、脱发的发生率,两用药方案之间均无统计学差异(P>0.05)。结论:XELOX方案不会明显增加老年患者的不良反应,且老年患者(年龄<70岁时)在卡培他滨单药的基础上联合奥沙利铂DFS和OS都可以显著获益,当患者年龄≥70岁时候,仅有DFS获益,而OS则无法获益。

AIM:To investigate the efficacy and safety of the XELOX therapy(capecitabine plus oxaliplatin)versus capecitabine monotherapy in adjuvant chemotherapy for elderly patients with colorectal cancer.METHODS:This study included 195 elderly patients with early colorectal cancer(60-82 years old)who underwent R0 surgical resection from January 2010 to December 2017 in Zhengzhou People's Hospital.Patients received either adjuvant chemotherapy with capecitabine monotherapy or XELOX therapy after surgery(selective adjuvant chemotherapy based on patient ECOG score,physical status,physician assessment,patient tolerance,and willingness).The baseline clinical data were collected through the hospital case system and patients were followed up according to the trial protocol.Disease-free survival(DFS)and overall survival(OS)were analyzed by Kaplan-Meier survival analysis.Cox risk ratio model was established to evaluate the efficacy of different adjuvant chemotherapy regimens with the same risk factors.Adverse reactions above level 2(according to CTCAE 4.0)were recorded for safety analysis.RESULTS:The median follow-up of the study was 5.75 years(the follow-up time range:0.30-7.50 years).The efficacy was evaluated in 195 patients enrolled in the study.The median disease-free survival(mDFS)was 5.0 years in the overall patient population,and the mDFS in the XELOX group was 5.5 years,significantly higher than the mDFS of the capecitabine monotherapy group for 3.6 years(P=0.047,95%CI:2.06-5.14).The overall median overall survival(mOS)was 7.1 years,and the mOS of the XELOX group was 7.1 years,significantly higher than the median total of the capecitabine monotherapy group mOS 4.5 years(P=0.021,95%CI:3.30-5.70).With the same risk factors,when the patients were younger than 70 years old,both the DFS(HR=0.74,P=0.036)and OS(HR=0.78,P=0.041)patients could benefit from the XELOX regimen;when the patients≥70 years old,only DFS(HR=0.77,P=0.035)could benefit from the XELOX therapy.Regardless of the patient's comorbidities,the patient's DFS and OS benefit from the XELOX therapy.However,patient's DFS and OS can benefit from XELOX only when the number of lymph nodes examined was less than 12 nodes and the number of cycles of patients receiving adjuvant chemotherapy was≥6 cycles.In terms of adverse reactions,the incidence of neutropenia(61.54%vs.39.74%,P=0.003)and neurotoxicity(65.81%vs.0%)were significantly higher in the XELOX therapy than the capecitabine monotherapy regimen.Other adverse reactions such as diarrhea,stomatitis,thrombocytopenia,hand-foot syndrome,anemia,nausea and vomiting,increased AST/ALT,and hair loss were not significantly different between the two groups(P>0.05).CONCLUSION:The XELOX therapy does not significantly increase adverse events in elderly patients,and elderly patients(age<70 years old)who combine oxaliplatin on the basis of capecitabine can significantly benefit from DFS and OS,but when the patients were≥70 years old,only DFS can benefit,while OS cannot.