真实世界中转移性结直肠癌患者三线化疗再挑战的临床疗效

The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study

目的评价真实世界中转移性结直肠癌(mCRC)患者三线化疗再挑战的临床疗效。方法2013年1月至2020年12月于天津医科大学肿瘤医院经奥沙利铂和(或)伊立替康化疗后进展且三线接受化疗再挑战的mCRC患者95例,收集其临床病理资料、治疗相关信息、近期疗效、不良反应及生存资料。采用Kaplan-Meier法进行生存分析,采用Cox比例风险模型分析mCRC患者三线化疗再挑战的预后影响因素。结果95例患者中,三线治疗采用单纯化疗32例,化疗联合靶向治疗63例。83例患者采用双药化疗,其中35例为奥沙利铂再挑战,48例为伊立替康再挑战。12例(12.6%)患者采用三药化疗,其中5例因前线序贯应用奥沙利铂和伊立替康,三线治疗为奥沙利铂和伊立替康再挑战,7例前线仅使用过奥沙利铂,归于奥沙利铂再挑战。三线化疗再挑战的客观缓解率为8.6%(8/93),疾病控制率为61.3%(57/93),中位无进展生存时间(PFS)为4.9个月,中位总生存时间为13.0个月。常见的不良反应为白细胞减少(34.7%)、中性粒细胞减少(34.7%),以及恶心(32.6%)、呕吐(31.6%)等消化道不良反应。3~4级不良反应多见于骨髓抑制。多因素Cox回归分析显示,性别(HR=1.609,95%CI:1.016~2.548)、一线治疗的PFS+二线治疗的PFS(HR=0.598,95%CI:0.378~0.947)是mCRC患者三线化疗再挑战PFS的独立影响因素。结论mCRC患者三线治疗采用化疗再挑战安全有效,尤其是一线治疗和二线治疗PFS累计超过1年者,三线治疗选择化疗再挑战的疗效可能更优。

Objective To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer(mCRC)in the real world.Methods The clinicopathological data,treatment information,recent treatment efficacy,adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected.Survival curves were plotted with the Kaplan-Meier method,and the Cox proportional hazard model was used to analyze the prognostic factors.Results A total of 95 mCRC patients were included.Among them,32 patients(33.7%)received chemotherapy alone and 63 patients(66.3%)received chemotherapy combined with targeted drugs.Eighty-three patients were treated with dual-drug chemotherapy(87.4%),including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients.The remaining 12 patients were treated with triplet chemotherapy regimens(12.6%).Among them,as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments,their third-line therapy re-challenged both oxaliplatin and irinotecan;7 patients only had oxaliplatin prescription before,and these patients re-challenged oxaliplatin in the third-line treatment.The overall response rate(ORR)and disease control rate(DCR)reached 8.6%(8/93)and 61.3%(57/93),respectively.The median progression free survival(mPFS)and median overall survival(mOS)were 4.9 months and 13.0 months,respectively.The most common adverse events were leukopenia(34.7%)and neutropenia(34.7%),followed by gastrointestinal adverse reactions such as nausea(32.6%)and vomiting(31.6%).Grade 3-4 adverse events were mostly hematological toxicity.Cox multivariate analysis showed that gender(HR=1.609,95%CI:1.016-2.548)and the PFS of front-line treatments(HR=0.598,95%CI:0.378-0.947)were independent prognostic factors.Conclusion The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge,especially for patients with a PFS of more than one year in front-line treatments.