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50 mg/d服药4周,停药2周(50 mg/d 4/2组);30例患者采用37.5 mg/d连续口服(37.5 mg/d CDD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(PFS)为48周,中位总体生存期(0S)为92周.分组分析显示:既往伊马替尼剂量为400 mg/d者,其PFS和OS均优于既往伊马替尼剂量大于400 mg/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OS劣于外显子9突变者(中位OS:71比157周,P=0.008).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,50 mg/d 4/2组腹泻及手足综合征的发生情况较37.5 mg/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400 mg/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37.5 mg/d连续口服的用药方案安全性较好.

abstractsObjective 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 35 weeks 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 157 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 patients with imatinib-resistant GIST.After 400 mg/d imatinib treatment failure,sunitinib should be prescribed instead of increased dosage of imatinib.Patients with KIT exon 9 mutations present better prognosis than those with KIT exon 11 mutations.The protocol of sunitinib 37.5 mg/d CDD possesses better safety.