中华消化外科杂志
中華消化外科雜誌
중화소화외과잡지
CHINESE JOURNAL OF DIGESTIVE SURGERY
2013年
4期
280-284
,共5页
张信华%宋武%何裕隆%吴晖%蔡世荣%韩方海%詹文华
張信華%宋武%何裕隆%吳暉%蔡世榮%韓方海%詹文華
장신화%송무%하유륭%오휘%채세영%한방해%첨문화
胃肠道间质肿瘤%靶向治疗%舒尼替尼
胃腸道間質腫瘤%靶嚮治療%舒尼替尼
위장도간질종류%파향치료%서니체니
Gastrointesitnal stromal tumor%Targeted therapy%Sunitinib
目的 评价舒尼替尼治疗伊马替尼耐药的进展期胃肠道间质瘤(GIST)患者的临床疗效.方法 回顾性分析2008年3月至2012年6月中山大学附属第一医院收治的接受舒尼替尼治疗的45例伊马替尼治疗耐药的进展期GIST患者的临床病理资料.患者主要采用舒尼替尼37.5 mg/d的持续给药方案,对原发肿瘤组织标本进行c-kit和血小板源性生长因子受体α(PDGFRα)基因突变检测,治疗3个月后评价舒尼替尼的治疗疗效,并分析影响患者预后的因素.采用Kaplan-Meier法绘制生存曲线,单因素分析采用Log-rank检验,多因素分析采用COX回归模型.结果 45例患者接受舒尼替尼的中位治疗时间为11.0个月(4 ～37个月).治疗3个月后评价疗效为:临床完全缓解占15.6％ (7/45),部分缓解占8.9％ (4/45),疾病稳定占46.7％ (21/45),疾病进展占28.9％(13/45).临床(影像学)完全缓解的患者均为舒尼替尼治疗前接受手术切除全部转移病灶或肝脏单发病灶消融治疗的患者.舒尼替尼最常见的3级或以上不良反应为手足综合征和贫血.42例患者进行了c-kit和PDGFRα基因突变检测,其中c-kit基因外显子9突变9例,外显子11突变21例,未检测到基因突变者(野生型)12例.接受舒尼替尼治疗中位无进展生存时间为8.0个月(4.1 ～11.9个月),中位总生存时间为25.0个月(13.4 ～36.6个月).单因素分析结果显示:肿瘤原发部位及原发病灶c-kit基因突变状态分别是无进展生存和总体生存的预测因素(x2=5.967,6.622；7.965,8.765,P＜0.05)；多因素分析结果显示:只有肿瘤原发病灶c-kit基因突变状态是患者治疗后无进展生存和总体生存的独立预测因素(Wald=6.540,7.205,P＜0.05).c-kit基因外显子9突变和野生型患者无进展生存时间和总体生存时间都显著优于c-kit外显子11突变的患者,差异有统计学意义(x2=7.965,8.765,P＜0.05).结论 舒尼替尼37.5 mg/d的持续给药方案可有效治疗伊马替尼耐药的进展期GIST,原发病灶c-kit基因突变状态为外显子9突变或野生型的患者临床获益较外显子11突变患者更显著.
目的 評價舒尼替尼治療伊馬替尼耐藥的進展期胃腸道間質瘤(GIST)患者的臨床療效.方法 迴顧性分析2008年3月至2012年6月中山大學附屬第一醫院收治的接受舒尼替尼治療的45例伊馬替尼治療耐藥的進展期GIST患者的臨床病理資料.患者主要採用舒尼替尼37.5 mg/d的持續給藥方案,對原髮腫瘤組織標本進行c-kit和血小闆源性生長因子受體α(PDGFRα)基因突變檢測,治療3箇月後評價舒尼替尼的治療療效,併分析影響患者預後的因素.採用Kaplan-Meier法繪製生存麯線,單因素分析採用Log-rank檢驗,多因素分析採用COX迴歸模型.結果 45例患者接受舒尼替尼的中位治療時間為11.0箇月(4 ～37箇月).治療3箇月後評價療效為:臨床完全緩解佔15.6％ (7/45),部分緩解佔8.9％ (4/45),疾病穩定佔46.7％ (21/45),疾病進展佔28.9％(13/45).臨床(影像學)完全緩解的患者均為舒尼替尼治療前接受手術切除全部轉移病竈或肝髒單髮病竈消融治療的患者.舒尼替尼最常見的3級或以上不良反應為手足綜閤徵和貧血.42例患者進行瞭c-kit和PDGFRα基因突變檢測,其中c-kit基因外顯子9突變9例,外顯子11突變21例,未檢測到基因突變者(野生型)12例.接受舒尼替尼治療中位無進展生存時間為8.0箇月(4.1 ～11.9箇月),中位總生存時間為25.0箇月(13.4 ～36.6箇月).單因素分析結果顯示:腫瘤原髮部位及原髮病竈c-kit基因突變狀態分彆是無進展生存和總體生存的預測因素(x2=5.967,6.622；7.965,8.765,P＜0.05)；多因素分析結果顯示:隻有腫瘤原髮病竈c-kit基因突變狀態是患者治療後無進展生存和總體生存的獨立預測因素(Wald=6.540,7.205,P＜0.05).c-kit基因外顯子9突變和野生型患者無進展生存時間和總體生存時間都顯著優于c-kit外顯子11突變的患者,差異有統計學意義(x2=7.965,8.765,P＜0.05).結論 舒尼替尼37.5 mg/d的持續給藥方案可有效治療伊馬替尼耐藥的進展期GIST,原髮病竈c-kit基因突變狀態為外顯子9突變或野生型的患者臨床穫益較外顯子11突變患者更顯著.
목적 평개서니체니치료이마체니내약적진전기위장도간질류(GIST)환자적림상료효.방법 회고성분석2008년3월지2012년6월중산대학부속제일의원수치적접수서니체니치료적45례이마체니치료내약적진전기GIST환자적림상병리자료.환자주요채용서니체니37.5 mg/d적지속급약방안,대원발종류조직표본진행c-kit화혈소판원성생장인자수체α(PDGFRα)기인돌변검측,치료3개월후평개서니체니적치료료효,병분석영향환자예후적인소.채용Kaplan-Meier법회제생존곡선,단인소분석채용Log-rank검험,다인소분석채용COX회귀모형.결과 45례환자접수서니체니적중위치료시간위11.0개월(4 ～37개월).치료3개월후평개료효위:림상완전완해점15.6％ (7/45),부분완해점8.9％ (4/45),질병은정점46.7％ (21/45),질병진전점28.9％(13/45).림상(영상학)완전완해적환자균위서니체니치료전접수수술절제전부전이병조혹간장단발병조소융치료적환자.서니체니최상견적3급혹이상불량반응위수족종합정화빈혈.42례환자진행료c-kit화PDGFRα기인돌변검측,기중c-kit기인외현자9돌변9례,외현자11돌변21례,미검측도기인돌변자(야생형)12례.접수서니체니치료중위무진전생존시간위8.0개월(4.1 ～11.9개월),중위총생존시간위25.0개월(13.4 ～36.6개월).단인소분석결과현시:종류원발부위급원발병조c-kit기인돌변상태분별시무진전생존화총체생존적예측인소(x2=5.967,6.622；7.965,8.765,P＜0.05)；다인소분석결과현시:지유종류원발병조c-kit기인돌변상태시환자치료후무진전생존화총체생존적독립예측인소(Wald=6.540,7.205,P＜0.05).c-kit기인외현자9돌변화야생형환자무진전생존시간화총체생존시간도현저우우c-kit외현자11돌변적환자,차이유통계학의의(x2=7.965,8.765,P＜0.05).결론 서니체니37.5 mg/d적지속급약방안가유효치료이마체니내약적진전기GIST,원발병조c-kit기인돌변상태위외현자9돌변혹야생형적환자림상획익교외현자11돌변환자경현저.
Objective To investigate the efficacy of sunitinib in the treatment of patients with imatinibresistant advanced gastrointestinal stromal tumor (GIST).Methods The clinical data of 45 patients with imatinib-resistant advanced GIST who received the treatment of sunitinib (37.5 mg/d) at the First Affiliated Hospital of Sun Yat-Sen University from March 2008 to June 2012 were retrospectively analyzed.The mutation of c-kit and platelet-derived growth factor receptor α (PDGFRα) was detected,and the efficacy of imatinib was assessed after the treatment for 3 months,and factors influencing the survival were analysed.The survival rate was calculated using the Kaplan-Meier method,survival analysis was done using the one-way analysis of variance,and multivariate analysis was done using the COX regression model.Results The median time of treatment with sunitinib for the 45 patients was 11.0 months (range,4-37 months).The complete remission rate,partial response rate,rate of stabilized condition and disease progression rate were 15.6％ (7/45),8.9％ (4/45),46.7％ (21/45) and 28.9％ (13/45) after the treatment with sunitinib for 3 months.All the patients with clinical (imaging) complete remission received surgery for metastatic lesions or B-ultrasound guided ablation for single liver metastasis before the treatment with sunitinib.The most common grade 3 or 4 adverse reactions of sunitinib were hand-foot syndrome and anemia.C-kit and PDGFRα mutational analysis were carried out.C-kit exon 9 mutation was detected in 9 patients,c-kit exon 11 mutation in 21 patients,and no mutation was detected in 12 patients.The median progression-free survival time was 8.0 months (range,4.1-11.9 months),and the median overall survival time was 25.0 months (range,13.4-36.6 months).The results of univariate analysis showed that the primary lesion sites and mutational status of primary lesions were factors influencing the progression-free survival and overall survival (x2=5.967,6.622 ; 7.965,8.765,P ＜ 0.05).The results of multivariate analysis showed that only the mutational status of c-kit of primary lesions was the independent factor influencing the progression-free survival and overall survival (Wald =6.540,7.205,P ＜ 0.05).The progression-free survival and overall survival of patients with c-kit exon 9 mutation and patients with no gene mutation were significantly longer than patients with c-kit exon 11 mutation (x2 =7.965,8.765,P ＜ 0.05).Conclusion Sunitinib with a dosage of 37.5 mg/d could effectively treat patients with imatinib-resistant advanced GIST.A better survival is observed in patients with c-kit exon 9 mutation or with no gene mutation when compared with patients with c-kit exon 11 mutation.
