伊立替康联合顺铂或5-FU治疗UGT1A1＊28野生型TA6/6患者不良反应的比较

Comparison of irinotecan plus cisplatin versus irinotecan plus infusional fluorouracil/leucovorin in management of adverse events in patients with UGT1A1＊28 wild genotype

目的：比较尿苷二磷酸葡萄糖醛酸转移酶1A1（UGT1A1）＊28启动子为野生型的TA6/6患者在使用伊立替康（irinotecan，CPT-11）联合顺铂与CPT-11联合5-FU/亚叶酸钙治疗时不良反应方面的差异。方法根据采取的治疗方案将98例UGT1A1＊28野生型TA6/6患者分为CPT-11联合顺铂组（IP组，n＝47）和CPT-11联合5-FU/亚叶酸钙组（FOLFIRI组，n＝51），对患者进行UGT1A1＊28启动子多态性检测，比较不良反应差异。结果在总体3～4级不良反应方面，IP组的发生率（61.7%）明显高于FOLFIRI组（39.2%），且组间差异具有统计学意义（P=0.026）。在血液学不良反应方面，IP组3～4级白细胞减少、中性粒细胞减少、血小板减少和血红蛋白减少发生率分别为34.0%、51.1%、14.9%和8.5%，FOLFIRI组的发生率分别为11.8%、29.4%、2.0%、0，组间差异均有统计学意义（均P＜0.05）；在非血液学方面，FOLFIRI组3～4级迟发性腹泻发生率为9.8%，IP组未发生3～4级腹泻，两组间发生率的差异有统计学意义（P=0.028）。结论 UGT1A1＊28野生型TA6/6患者在接受CPT-11联合顺铂和CPT-11联合5-FU/亚叶酸钙两种化疗方案治疗的不良反应谱存在差异；应用CPT-11时，不但要考虑到UGT1A1＊28启动子多态性对不良反应的影响，而且还要考虑CPT-11联合不同药物出现不良反应情况。

Objective To investigate the difference regarding adverse events management between irinotecan （CPT-11） plus cisplatin or plus fluorouracil/leucovorin in patients with UGT1A1＊28 wild genotype （TA6/6）. Method Genomic DNA was extracted from peripheral blood to identify the UGT1A1＊28 wild genotype （TA6/6） in patients treated with both irinotecan-contained chemotherapy. Irinotecan plus cisplatin （IP group, n=47） and irinotecan plus flu-orouracil/leucovorin （FOLFIRI group, n=51） were compared in patients with UGT1A1＊28 wild genotype TA6/6. c2 test was used to investigate the difference of toxicity between IP group and FOLFIRI group. Result The overall inci-dence of grade 3 or 4 toxicity was higher in IP group than in FOLFIRI group （61.7% vs 39.2%; HR=1.57, 95%CI：1.045-2.369; P=0.026）. Serious hematological toxicity was also higher in IP group compared with the FOLFIRI group in respect of grade 3/4 neutropenia （51.1% vs 29.4%, P=0.029）, grade 3/4 anemia （8.5% vs 0, P=0.033） and grade 3/4 thrombocytopenia （14.9% vs 2.0%, P=0.019）. However, grade 3/4 delayed diarrhea was more common in FOLFIRI group than in IP group （9.8% vs 0, P=0.028）. Conclusion The adverse events profile was different in IP- and FOL-FIRI-treated patients with UGT1A1＊28 wild genotype （TA6/6）. As in CPT-11 administration, not only the polymor-phism of UGT1A1＊28 promotor, but also the adverse events profile of CPT-11 in combination with different medica-tion should be considered.