舒尼替尼治疗伊马替尼耐药胃肠间质瘤的疗效及安全性分析  

Efficacy and safety of sunitinib on patients with imatinib-resistant gastrointestinal stromal tumor

作　　者：刘星[1] 蒋伟忠[1] 官国先[1] 陈致奋[1] 池畔[1] 卢辉山[1] 

机构地区：[1]福建医科大学附属协和医院胃肠外科,福州350001

出　　处：《中华胃肠外科杂志》2013年第3期221-225,共5页Chinese Journal of Gastrointestinal Surgery

摘　　要：目的探讨舒尼替尼治疗伊马替尼耐药胃肠间质瘤（GIST）的疗效及安全性。方法回顾性分析2008年5月至2012年4月间在福建医科大学附属协和医院接受舒尼替尼治疗的48例伊马替尼耐药GIST患者的临床资料。舒尼替尼用药方案：18例患者采用50mg／d服药4周，停药2周（50mg／d4／2组）；30例患者采用37．5mg／d连续口服（37．5mg／dCDD组）。结果48例患者舒尼替尼中位治疗时间为56周．按Choi标准于治疗后24周进行近期疗效评估．获完全缓解1例，部分缓解12例，疾病稳定21例，疾病进展14例，客观有效率为27．1％（13／48），疾病控制率为70．8％（34／48）。48例患者中位随访时间为89周，中位无进展生存期（PLUS）为48周，中位总体生存期（OS）为92周。分组分析显示：既往伊马替尼剂量为400mg／d者，其PFS和Os均优于既往伊马替尼剂量大于400mg／d者（中位PFS：53比35周，P=0．018；中位OS：157比71周，P=0．003）；外显子11突变者0s劣于外显子9突变者（中位0s：71比157周，P=O．008）。治疗期间的主要不良反应有手足综合征（25例，52．1％）、恶心（24例，50．0％）、疲乏（23例，47．9％）和中性粒细胞减少（21例，43．7％）。按舒尼替尼给药方案分组分析，50mg／d4／2组腹泻及手足综合征的发生情况较37．5mg／dCDD组更为严重（P=0．027，P=0．048）。结论舒尼替尼治疗伊马替尼耐药的GIST疗效较好。在伊马替尼400mg／d耐药后应直接换用舒尼替尼而不要加大伊马替尼用药剂量。外显子9突变者舒尼替尼的治疗效果优于外显子11突变者。舒尼替尼37．5mg／d连续口服的用药方案安全性较好。Objective To investigate the efficacy and safety of sunitinib on the management of gastrointestinal stromal tumors （GIST） patients with imatinib resistance. Methods Clinical data of 48 patients with imatinib-resistant GIST received sunitinib therapy from May 2008 to April 2012 in the Union Hospital of Fujian Medical University were analyzed retrospectively. Eighteen patients received 50 mg/d of sunitinib in a protocol of 4/2（4 weeks on and 2 weeks off）[50 mg/d （4/2）], and 30 patients received a protocol of 37.5 mg of sunitinib continuous daily dose （37.5 mg/d CDD）. Results The median duration of sunitinib administration of all the 48 patients was 56 weeks, and the short-term efficacy was evaluated at 24 weeks after the initial treatment according to the Choi criteria. The response rate was 27.1%（13/48）, including 1 case with complete response（CR）, 12 cases with partial response （PR）, and 21 cases with stationary disease （SD）. The disease control rate was 70.8%（34/48）. The mean follow-up time of 48 patients was 89 weeks. The median progression-free survival （PFS） and overall survival （OS） were 48 weeks and 92 weeks respectively. Stratified analyses indicated that the median PFS of patients previously treated by imatinib 400 mg/d and 〉400 mg/d were 53 weeks and 35weeks respectively （P=0.018）, and the median OS of these two groups were 157 weeks and 71 weeks respectively （P=0.003）. Patients with exon 11 mutations had a significantly shorter OS compared with those with exon 9 mutations （71 weeks vs I5T weeks, P=0.008）. Hand-foot syndrome was the most common adverse effect （25/48, 52.1%）, followed by nausea （24/48, 50.0%）, fatigue （23/48, 47.9%）, neutropenia （21/48, 41.7%）. The sub-group analysis of two protocols of sunitinib administration showed that the incidence of diarrhea and hand-foot syndrome were higher in 50 mg/d （4/2） group than those in 37.5 mg/d CDD group （P=0.027, P=0.048）. Conclusions Sunitinib is effective for the patient

关 键 词：胃肠间质瘤 舒尼替尼 伊马替尼耐药 治疗效果 生存期 不良反应 

分 类 号：R735.2[医药卫生—肿瘤] R735.3[医药卫生—临床医学]