目的 观察替吉奥胶囊联合奥沙利铂治疗晚期结直肠癌的近期疗效和毒性反应。 方法 2011年5月-12月,将30例晚期结直肠癌患者根据体表面积来确定初始剂量,体表面积<1.25 m2者,替吉奥胶囊40 mg/次,2次/d;体表面积1.25~1.50 m2者,替吉奥胶囊50 mg/次,2次/d;体表面积>1.50 m2者,替吉奥胶囊60 mg/次,2次/d。早饭后和晚饭后分别口服1次,第1~4天服用奥沙利铂注射液 130 mg/ m2,静脉滴注,第1、21天重复,此为1个月周期。连用2周期后,按美国国立癌症研究所拟定的药物不良反应的分级评价标准3.0版本评价不良反应,按实体瘤治疗疗效评价标准评价疗效。 结果 30例患者中,完全缓解1例(3.3%),部分缓解7例(23.3%),稳定12例(40%),进展10例(33.3%),疾病控制率为66.6%。不良反应主要是血液学毒性、胃肠道反应、皮肤色素沉着及外周神经毒性;1例Ⅳ度骨髓抑制,3例3度贫血,2例3度腹泻,2例3度皮肤色素沉着,2例3度恶心、呕吐,其余且均在Ⅰ~Ⅱ度骨髓抑制。 结论 替吉奥胶囊联合奥沙利铂方案治疗晚期结直肠癌可获得较高的疾病控制率,不良反应可控。
ObjectiveTo understand the effect of programmed death-1 (PD-1) inhibitors on defective mismatch repair (dMMR) / microsatellite instability-high (MSI-H) advanced colorectal cancer (CRC). MethodThe literature of recent research relevant PD-1 inhibitors in the utility for patients with dMMR/MSI-H advanced CRC was reviewed and summarized. ResultsAt present, there were many studies exploring the utility of anti-PD-1 inhibitors for the treatment of dMMR/MSI-H advanced CRC (including locally advanced CRC and metastatic CRC), and some studies were still in trials. Studies had consistently shown that the use of PD-1 inhibitors in dMMR/MSI-H advanced CRC as first-line or subsequent therapy, as well as in the neoadjuvant setting, leading to significant survival benefits. These benefits were particularly notable in cases of dMMR/MSI-H metastatic CRC with concurrent BRAF/RAS mutations and in the context of neoadjuvant immunotherapy aimed at organ preservation in locally advanced dMMR/MSI-H CRC. Moreover, there were numerous studies exploring “dual immunotherapy”, and most studies found that its efficacy was superior to that of single immunotherapy. However, the more adverse events were reported by the “dual immunotherapy” compared to the single immunotherapy. ConclusionsOverall, based on results of the literature reviewed, PD-1 inhibitors have shown significant clinical benefits in dMMR/MSI-H advanced CRC, but there are still more issues that need to be further explored, such as discovering more first-line PD-1 inhibitors, overcoming drug resistance and adverse events. Future clinical practice should prioritize more precise individualized identification and the application of more effective combination therapy regimens to further optimize outcomes for patients with dMMR/MSI-H advanced CRC.