伊立替康化疗相关性腹泻发生的特点与危险因素分析

目的:探讨伊立替康化疗相关性腹泻发生的特点与危险因素,提高伊立替康临床应用安全性。方法:收集2014年1月至2016年6月以伊立替康为基础的化疗方案治疗的肿瘤患者信息,分析患者性别、年龄、烟酒史、原发灶部位、伊立替康剂量、UGT1A1基因多态性等临床特征与腹泻发生率、腹泻严重程度的关系,总结伊立替康致化疗相关性腹泻的危险因素。结果:共175例使用含伊立替康方案化疗的患者纳入分析,男性105例,女性70例,腹泻发生率为25.7%(45/175),其中早发性腹泻7例(4.0%),迟发性腹泻38例(21.7%);轻中度腹泻(I～II级) 36例(20.6%),严重腹泻(III～IV级) 9例(5.1%)。严重腹泻均为迟发性腹泻,发生于给药后5～14 d。高龄(≥65岁)是腹泻发生的危险因素(P=0.02);伊立替康联合铂类化疗时严重腹泻发生率为17.0%(8/47),高于FOLFIRI方案(P=0.003);联合奥沙利铂化疗的严重腹泻率为40%(4/10),高于联合其他铂类,但无统计学差异(P=0.22);患者性别、烟酒史、原发灶部位、伊立替康剂量、UGT1A1基因多态性对腹泻发生率和发生的严重程度无影响。结论:高龄(≥65岁)患者使用伊立替康为主的化疗方案治疗时发生腹泻的风险较高,伊立替康联合铂类化疗时需警惕严重腹泻的发生。

Analysis on characteristics and risk factors of irinotecan chemotherapy induced diarrhea

OBJECTIVE To explore the characteristics and relative risk factors of irinotecan-induced diarrhea, and improve the safety profiles of irinotecan in clinical use.METHODS Demographics, baseline characteristics and clinical responses of patients treated with irinotecan in our hospital were collected from January 2014 to June 2016. Subsequently, relationships between incidence or severity of diarrhea and gender, age, history of cigarette smoking and alcohol drinking, disease types, dose of irinotecan, UGT1A1 gene polymorphism were analyzed statistically by SPSS.RESULTS Totally 175 cases were collected, including 105 male and 75 female patients. Total incidence of irinotecan-induced diarrhea was 25.7% (45/175), 7 (4.0%) of which were early onset diarrhea and the rest 38 (21.7%) cases were delayed incidences. In terms of severity, 36 of the 45 cases (20.6%) were grade 1-2 diarrhea and 9 (5.1%) cases were grade 3-4 diarrhea. Notably, all of the grade 3-4 diarrhea were delayed diarrhea, which occurred after 5 to 14 days of medication. Age was a significant risk factor in patients 65 years old and above, who showed higher incidences of diarrhea (P=0.02). Combination chemotherapy with platinum also showed a statistically significant higher rate (17%, 8/47) of serious diarrhea than FOLFIRI regimen (P=0.003), but combination with oxaliplatin only showed a numerically higher while statistically insignificant incidence rate (40%, 4/10) of serious diarrhea (P=0.22). All the other clinical characteristics including gender, history of cigarette smoking and alcohol drinking, tumor type, dose of irinotecan and UGT1A1 gene polymorphism did not show any significant influence on the incidence or severity of diarrhea.CONCLUSION Diarrhea induced by irinotecan occurs at a higher risk in patients above or equal to 65, and intensive care should be taken to the occurrence of serious diarrhea with combination chemotherapy of irinotecan plus platinum.