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

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.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。.