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

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。

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

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 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 orotocol of sunitinib 37.5 mg/d CDD nossesses better safety.