分析雷替曲塞联合伊立替康治疗晚期结直肠癌的疗效及安全性。

纳入中国医学科学院肿瘤医院内科2015年1月至2018年12月收治的34例既往一线或二线使用含氟尿嘧啶类化疗方案失败的晚期结直肠癌患者，接受雷替曲塞联合伊立替康方案治疗，主要观察终点为客观有效率（ORR），次要观察终点包括疾病无进展生存时间（PFS）、总生存时间（OS）、疾病控制率（DCR）和安全性。

34例患者病理确诊均为结直肠腺癌。近期疗效中观察到部分缓解（PR）为6例，疾病稳定（SD）为25例，疾病进展（PD）为3例，客观有效率（ORR）为17.6%（6/34），疾病控制率（DCR）为91.2%（31/34）。其中，二线患者ORR为21.7%（5/23），DCR为91.3%（21/23）；三线患者ORR为9.1%（1/11），DCR为90.9%（10/11）。34位患者全部追踪至疾病进展，疾病无进展中位生存时间（mPFS）为180天（95% CI：157.2~202.8），截止2020年2月27日末次随访未观察到中位总生存时间（mOS），平均OS（389.0±51.1）天。其中，接受二线治疗患者的mPFS为193天，平均OS（412.0±61.5）天。接受三线治疗患者的mPFS为150天，mOS为311天。治疗后肿瘤标志物CEA与CA19-9水平均有降低，其中CA19-9治疗前后平均水平为（169.8±48.0）U/mL和（143.8±57.7）U/mL（t=0.700，P=0.655）。CEA治疗前平均水平为（255.0±40.6）ng/mL，治疗后为（104.2±32.4）ng/mL，下降趋势经比较差异具有统计学意义（t=1.759，P=0.001）。安全性方面，常见不良反应包括恶心呕吐、腹泻、白细胞及中性粒细胞减少、血红蛋白降低和转氨酶升高等，多为Ⅰ~Ⅱ级，Ⅲ级不良反应有中性粒细胞减少（2/34）、白细胞减少（1/34）和转氨酶升高（1/34），无Ⅳ级不良反应及化疗相关死亡事件发生。

雷替曲塞联合伊立替康治疗晚期结直肠癌疗效确切，安全性良好。其中二线治疗ORR与国内外既往研究相似，但不良反应更低，值得临床进一步推广应用。

To evaluate the efficacy and safety of raltitrexed combind with irinotecan in patients with metastatic colorectal cancer (mCRC).

Between January 2015 and December 2018, a total of 34 patients with mCRC after the failure of first-line or second-line chemotherapy were selected and treated with raltitrexed plus irinotecan in Cancer Hospital Chinese Academy of Medical Sciences. The primary endpoint was objective response rate (ORR), and the secondary endpoints were disease control rate (DCR), progress-free survival (PFS), overall survival (OS) and safety.

The pathology of 34 patients was adenocarcinoma. There were 16 patients (47.1%) with rectal cancer, followed by 10 cases (29.4%) in the left colon and 8 cases (23.5%) in the right colon. Thirty patients (88.2%) accepted undergone surgical treatment. Six achieved a partial response (PR), Twenty-five had a stable disease (SD) and 3 had a progressive disease (PD). The ORR was 17.6% (6/34), and the DCR was 91.2% (31/34). For second-line treatment, the ORR was 21.7% (5/23), DCR was 91.3% (21/23). For third-line treatment, the ORR was 9.1% (1/11), DCR was 90.9% (10/11). All patients were defined progression of disease, the median progression free survival (mPFS) was 180 days(95% CI: 157.2~202.8). The median overall survival (mOS) was not observed at the last follow-up. The average OS was (389±51.1)days. the median PFS of patients receiving second-line treatment was 193 days, with an average OS of (412±61.5)days. Patients receiving third-line treatment had mPFS of 150 days and mOS of 311 days. The levels of tumor markers CEA and CA19-9 decreased after treatment. The average levels of CA19-9 before and after treatment were 169.8±48.0 U/mL and 143.8±57.7 U/mL (t=0.700, P=0.655). The average level of CEA before treatment was (255.0±40.6) ng/mL and (104.2±32.4) ng/mL after treatment, the decline has statistically significant (t=1.759, P=0.001). The main adverse reactions were nausea, vomiting, diarrhea, leucopenia, neutropenia, hemoglobin reduction and transaminase elevation, mostly grade I or II. Grade III adverse reactions included leucopenia (2/34), anemia (1/34) and transaminase elevation (1/34). There were no grade IV adverse reactions and treatment-related deaths.

The combination of raltitrexed combined with irinotecanas second-line and above treatment could be an efficient and safe option for patients with mCRC. Particularly, it has presented encouraging ORR and lower toxicities as second-line therapy, which is worthy of further clinical application.