胃肠间质瘤68例

目的探讨胃肠道间质瘤（GIST）的临床特点、诊断、治疗及预后。方法回顾性分析68例GIST的临床病理及随访资料。结果GIST部位：胃41例，肠26例，大网膜1例。62例行外科手术切除，6例行姑息性切除。8例术后1年内复发再手术，未行辅助治疗。6例姑息术后患者及12例术后复发者给予甲磺酸伊马替尼200～600mg／d口服，患者获益率（CR＋PR＋SD）83-3％，获益者中位无进展生存期（TTP）超过14个月。结论GIST以胃及小肠多见，目前治疗仍以手术切除为主，手术切除辅以分子靶向药物甲磺酸伊马替尼，可延长患者生存期。     

甲磺酸伊马替尼治疗不能切除和/或转移的胃肠道间质瘤的临床分析

目的：评价甲磺酸伊马替尼(ST1571)治疗不能手术切除和／或转移的胃肠道间质瘤疗效和毒性。方法：口服甲磺酸伊马替尼400mg/日治疗10例不能手术切除和／或转移的胃肠道间质瘤患者。结果：9例可评价疗效，4例部分缓解，4例稳定。10例评价不良反应，非血液学毒性有水肿(主要是眼眶周围水肿)、腹痛、腹泻、恶心呕吐、乏力、腹腔肿瘤出血、间歇性肌肉痉挛和结膜炎，大多为I～Ⅱ度。血液学毒性少见。结论：酪氨酸激酶抑制剂甲磺酸伊马替尼治疗不能手术切除和／或转移的胃肠道间质瘤有一定疗效，且毒性可耐受。     

苹果酸舒尼替尼二线治疗国人晚期胃肠间质瘤的临床观察

的 探讨苹果酸舒尼替尼二线治疗甲磺酸伊马替尼治疗失败的国内胃肠间质瘤（GIST）患者的疗效和安全性,并初步分析后续治疗对生存的影响。方法 回顾性分析2008年11月至2009年12月应用舒尼替尼二线治疗伊马替尼失败的24例GIST患者资料,口服舒尼替尼50mg／日,连续4周,停药2周,6周为1周期。按照RECIST 1.1版进行疗效评价,根据NCI CTC 3.0版进行毒性评价。结果 24例患者共接受治疗232个周期,平均9.7个周期（2～29个周期）。获PR 6例,SD 12例,PD 6例,有效率为 25％,疾病控制率为75％。舒尼替尼二线治疗进展后有8例接受后续治疗。中位随访时间为378天（190～1554天）,中位无进展生存时间（PFS）为336天（95％CI：223.2～448.8天）,中位总生存时间（OS）为655天（95％CI：359.7～950.3天）。其中未接受后续治疗组的中位OS为392天（95％CI： 190.1～593.9天）,接受后续治疗组的中位OS为1303天（95％CI：661.2～1544.8天）,两组差异有统计学意义（P=0.000）。毒副反应多为1～2级,未发生治疗相关性死亡。结论 舒尼替尼二线治疗伊马替尼失败的国内GIST患者有效,不良反应轻微,安全可控;对于二线治疗失败的患者采取后续治疗可能有生存获益。     

舒尼替尼治疗伊马替尼治疗失败或不能耐受GIST的毒副反应及其防治

目的 探讨舒尼替尼(索坦)治疗甲磺酸伊马替尼治疗失败或不能耐受的胃肠间质瘤(GIST)患者的毒副反应情况及其防治措施.方法2009年1月至201 1年1月索坦治疗甲磺酸伊马替尼治疗失败或不能耐受的GIST患者41例,其中男性24例,女性17例,平均年龄55.5岁(29～82岁).29例口服索坦50mg/日,5例口服索坦...     

胃肠间质瘤近代治疗中的若干问题

 胃肠间质瘤（GIST）是来源于消化道的间质肿瘤,靶向药物伊马替尼的出现改变了GIST的整个治疗模式,由传统的外科手术单一模式向综合应用靶向治疗、外科治疗和腔镜外科治疗的个体化治疗模式转变。文章就近年来GIST在术前活组织病理检查、腔镜外科治疗、伊马替尼新辅助治疗及伊马替尼疗效评价方面的进展作一介绍。     

伊马替尼新辅助治疗直肠间质瘤的疗效及安全性分析

目的 探讨甲磺酸伊马替尼新辅助治疗原发直肠胃肠间质瘤（GIST）的疗效及安全性。方法40例直肠GIST患者口服甲磺酸伊马替尼片400mg/天, 连续口服6个月后评估手术指征。根据肿瘤大小和位置分别采用局部切除术、直肠低位前切除术和腹会阴联合直肠癌根治术。结果按RECIST 1.1版标准评价,获CR 3例,PR 31例,SD 4例,PD 2例;有效率（RR）为850%,疾病控制率（DCR）为95.0%;按Choi标准评价,获CR 3例,PR 28例,SD 7例,PD 2例;RR为77.5%,DCR为95.0%。治疗后获R0切除38例。40例患者的1年生存率为1000%,2年生存率为950%。不良反应以轻度水肿发生率最高,为72.5%,其次为白细胞减少（47.5%）;其他不良反应包括乏力、腹痛、胃肠道反应等,均可耐受。结论 直肠GIST患者术前使用甲磺酸伊马替尼辅助治疗,能够扩大患者的手术指征,提高R0切除率,疗效确切,安全性高,可以作为直肠GIST个体化治疗方案之一。     

16例巨大型胃肠间质瘤手术治疗分析

目的：通过对巨大型胃肠间质瘤（GIST）的诊断和手术方式进行探索,为临床治疗巨大型 GIST 提供新思路。方法对16例巨大型 GIST 患者一般资料、影像学资料、手术方式、随访指标进行回顾性调查,并进行统计学分析。结果11例服用甲磺酸伊马替尼患者无复发生存期1 a 以上,而5例未服用伊马替尼治疗患者1 a 内复发,中位无复发生存期为33个月。COX 多因素分析显示,肿瘤部位、术中肿瘤有无破裂、是否使用伊马替尼治疗与患者预后有关（P <0.05）,可作为患者预后的独立因素。结论巨大型 GIST 在选择手术时,应遵循术前影像学评估、术前服用甲磺酸伊马替尼治疗缩小肿瘤和手术切除时边缘切净为3大原则,这对于改善患者预后和延长生存期有益。     

不可切除或转移性胃肠道间质瘤患者甲磺酸伊马替尼治疗前后血清成纤维细胞生长因子2的变化

 目的　探讨不可切除或转移性胃肠道间质瘤患者甲磺酸伊马替尼治疗前后血清成纤维细胞生长因子2（FGF2）水平变化。方法　应用酶联免疫吸附法（ELISA）检测27例不可切除或转移性胃肠道间质瘤患者甲磺酸伊马替尼治疗前后血清FGF2,并进行比较。结果　治疗前血清FGF2阳性率为63.0 %（17／27）,经甲磺酸伊马替尼治疗3个月后降为33.3 %（9／27）,二者间差异有统计学意义（χ2＝4.08,P＝0.039）。伊马替尼治疗3个月后复查CT,无完全缓解 ,部分缓解率51.9 %（14／27）,稳定率48.1 %（13／27）,无进展病例。结论　不可切除或转移性胃肠道间质瘤患者血清FGF2阳性率升高,甲磺酸伊马替尼治疗可以降低不可切除或转移性胃肠道间质瘤患者血清FGF2水平。     

49例胃肠间质瘤的治疗及预后

目的探讨胃肠间质瘤（GIST）的治疗方法及预后因素。方法收集1990年7月至2007年7月收治的49例GIST患者的完整临床资料并进行分析。结果手术治疗47例,2例不能手术者及11例术后危险分级为恶性者口服伊马替尼治疗。术后服药者5年总体生存率64．7％,单纯服药者2年生存率为50．0％。免疫指标阳性率与肿瘤发生部位及恶性程度不相关（P〉0．05）。结论手术切除是GIST最主要的治疗手段,伊马替尼治疗是不可切除或转移的GIST患者的最佳选择,合理治疗及充分认识相关影响因素可以提高GIST的预后。     

甲磺酸伊马替尼治疗胃肠道间质瘤的研究进展

胃肠道间质瘤（GIST）是胃肠道及腹腔最常见的间叶源性肿瘤,对常规的放疗、化疗均不敏感。外科手术是局限性GIST患者的主要治疗方式,但术后复发率较高。对于术前、术后辅助、复发、转移及不能手术切除的患者,酪氨酸激酶抑制剂甲磺酸伊马替尼对其有较好的治疗效果。本文对甲磺酸伊马替尼治疗胃肠道间质瘤的研究进展作一综述。     

Efficacy and safety profile of imatinib mesylate (ST1571) in Japanese patients with advanced gastrointestinal stromal tumors: a phase II study (STI571B1202)

BACKGROUND: Imatinib mesylate, an inhibitor of KIT, ABL protein, and platelet-derived growth factor receptor alpha (PDGFRalpha) tyrosine kinase, has recently been found to have a dramatic antitumor effect on gastrointestinal stromal tumor (GIST). The aim of this study was to assess the efficacy and safety of imatinib mesylate in Japanese patients with advanced GIST. METHODS: Patients with measurable lesions were enrolled between April 1, 2002, and September 20, 2002, using a design based on previous phase II studies in the United States and the European Union. The diagnosis of GIST was proven histologically with positive immunostaining for KIT (CD117). Imatinib mesylate was administered at a dose of either 400 mg or 600 mg once a day. Pharmacokinetic parameters and mutation analysis of c-kit were also assessed in a subgroup of patients. RESULTS: A total of 74 patients (28 receiving imatinib mesylate at 400 mg/day; 46 receiving 600 mg/day); median age, 56.0 years, were enrolled. No patient had a complete response, 51 patients (69%) had a partial response, and 19 patients (26%) had stable disease. The median progression-free survival time was 96 weeks. The estimated 3-year overall survival (Kaplan-Meier) rate for all patients was 73.6%. The most frequent adverse effects related to the drug were nausea (78%), diarrhea (70%), dermatitis (62%), facial edema (61%), edema of the lower limbs (58%), vomiting (54%), and eyelid edema (51%). Most of the adverse effects were mild and manageable. CONCLUSION: Imatinib mesylate is generally safe and has significant activity in the treatment of advanced GIST in Japanese patients.     

甲磺酸伊马替尼治疗晚期隆突性皮肤纤维肉瘤的临床研究

目的 评价晚期隆突性皮肤纤维肉瘤(DFSP)患者应用甲磺酸伊马替尼的疗效和不良反应.方法 2004年11月至2009年10月,应用甲磺酸伊马替尼(400 mg,口服,每日1次)治疗晚期有随访资料的DFSP患者24例,其中二线治疗2例,三线或三线以上治疗22例,对其疗效、不良反应和生存时间进行分析.结果 全组24例患者均可评价疗效,其中完全缓解(CR)8例,占33.3%;部分缓解(PR)10例,占41.7%;稳定(SD)2例,占8.3%;进展(PD)4例,占16.7%.全组患者的疾病控制率为83.3%.获得CR和PR的18例患者的中位缓解时间为5.6个月.疾病控制(CR+PR+SD)者的中位生存时间为30个月,无效(PD)者的中位生存时间为10个月,二者差异有统计学意义(P＜0.001).与甲磺酸伊马替尼治疗相关的不良反应为恶心呕吐(20.8%)、中性粒细胞减少(12.5%)和水肿(8.3%)等,多为轻至中度.结论 甲磺酸伊马替尼治疗中国晚期DFSP患者的有效率高,耐受性好;推荐剂量为400 mg,每日1次.

Abstract：

Objective To evaluate the efficacy, side effects and toxicity of imatinib mesylate in the treatment of patients with locally advanced and/or metastatic dermatofibrosarcoma protuberans (DFSP). Methods Twenty-four cases of advanced DFSP diagnosed by pathology and treated in our hospital from Nov. 2004 to Oct. 2009 were included in this study. The patients were treated with imatinib mesylate (dosage: 400 mg, po, qd) and carefully observed for treatment efficacy, side effects and survival time. There were 2 patients taking the drug as second line therapy, and other 22 patients as third or more than third line therapy. Results The 24 patients were evaluable for the efficacy. There were 8 patients (33.3%) with CR, 10 pts (41.7%) PR, 2 patients (8.3%) SD, and 4 patients (16.7%) PD. The disease control rate (DCR＝CR+PR+SD) was 83.3%. The median response time in 18 cases with CR and PR was 5.6 months. The median survival time in 20 cases with disease control was 30 months, however, that in nonresponse (PD) cases was only 10 months. Side reactions related to imatinib mesylate included nausea and vomiting (20.8%), neutropenia (12.5%), and edema (8.3%). Conclusions Our results are consistent with previous reports in the literature. Imatinib is a safe and effective moleucular target drug used for Chinese. Only mild adverse reactions occur in the treated patients. It is worth using imatinib in the treatment of advanced DFSP patients.     

Neoadjuvant and adjuvant therapy with imatinib for locally advanced gastrointestinal stromal tumors in eastern Indian patients

Background: Imatinib mesylate is able to at least modify the course of gastrointestinal stromal tumours (GISTs). Neoadjuvant use for locally advanced lesions is evolving as a new treatment paradigm in this hitherto universally fatal disease. Methods and Results: The study patients with locally advanced GIST received neoadjuvant and adjuvant imatinib mesylate. Response was noted as per the RECIST protocol and overall progression free survival was reported. Of 19 patients (mean age 38.5 years, range 26 yrs to 64 yrs) studied, 13 achieved partial response (PR) and 6 a stationary disease (SD) on preoperative imatinib. Histopathological evaluation and grading of responses revealed only moderate and low grade pathological response after imatinib. R0 resection was possible in 13/19 and R1 in 6/19. Imatinib was well tolerated and adverse reactions were minimal. Post operative complications of surgery were not out of the ordinary for a surgical series featuring extensive abdominal surgery. Conclusion: Preoperative imatinib in locally advanced GIST seems to be a reasonable option for locally advanced GIST patients and enough downstaging to allow a resection with microscopically negative margins can be expected in a fairly good proportion of patients.     

Imatinib induced severe skin reactions and neutropenia in a patient with gastrointestinal stromal tumor

Background

Imatinib mesylate has been used for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST). The current recommended dose of imatinib is 400 mg/day that is increased to 800 mg/day in cases with disease progression. However, imatinib can be associated with diverse adverse events, which has limited its use. We report a case of severe adverse skin reactions with neutropenic fever during imatinib treatment in a patient with GIST.

Case presentation

A 71-year-old man was admitted with a one month history of epigastric pain and a palpable mass in the right upper quadrant. An abdominal CT scan revealed a 20 × 19 cm intraabdominal mass with tumor invasion into the peritoneum. Needle biopsy was performed and the results showed spindle shaped tumor cells that were positive for c-KIT. The patient was diagnosed with unresectable GIST. Imatinib 400 mg/day was started. The patient tolerated the first eight weeks of treatment. However, about three months later, the patient developed a grade 4 febrile neutropenia and a grade 3 exfoliative skin rash. The patient recovered from this serious adverse events after discontinuation of imatinib with supportive care. However, the skin lesions recurred whenever the patient received imatinib over 100 mg/day. Therefore, imatinib 100 mg/day was maintained. Despite the low dose imatinib, follow up CT showed a marked partial response without grade 3 or 4 toxicities.

Conclusion

The recommended dose of imatinib for the treatment of GIST is 400 mg/day but patients at risk for adverse drug reaction may benefit from lower doses. Individualized treatment is needed for such patients, and we may also try sunitinib as a alternative drug.     

Simultaneously occurring chronic myelogenous leukemia and gastrointestinal stromal tumors treated with imatinib

Imatinib mesylate (imatinib, STI571, Gleevec; Novartis Pharma) is an orally administered competitive inhibitor of BCR-ABL tyrosine kinase that has demonstrated significant efficacy in chronic myelogenous leukemia (CML). Imatinib is also a potent inhibitor of the receptor-type KIT tyrosine kinase with demonstrated benefits in KIT-expressing gastrointestinal stromal tumors (GISTs). This article presents the case of a patient with simultaneous occurrence of CML and GIST who was treated with the single agent imatinib. To our knowledge, this is the first report of simultaneous occurrence of these two malignancies and of the efficacy of imatinib in concurrent treatment of both neoplasms in a single patient.     

甲磺酸伊马替尼治疗手术无法切除的晚期胃肠间质瘤

目的:探讨甲磺酸伊马替尼用于治疗晚期胃肠间质瘤的疗效及生存获益。方法:收集2004年9 月至2015年6 月天津医科大学肿瘤医院收治的无法手术切除的61例晚期胃肠间质瘤患者的临床资料,接受初始剂量400 mg/d 的口服甲磺酸伊马替尼治疗,定期随访,评价生存获益及药物不良反应。结果:61例患者开始接受治疗1 年后,治疗有效率为57.4%（35/ 61）,疾病控制率为88.5%（54/ 61）,Logic二元回归分析显示性别、年龄和腹盆腔多发病灶是影响治疗有效率的因素（P < 0.05）。 本组患者5 年累积生存率为53% ,Cox 回归模型分析提示腹盆腔的多发病灶是影响患者生存获益的重要因素（P < 0.05）。 除2 例患者出现出血,其余患者不良反应轻微。结论:甲磺酸伊马替尼显著改善晚期胃肠间质瘤的生存获益,可作为无法手术切除的晚期胃肠间质瘤的首选治疗。      

Adherence to imatinib therapy in patients with gastrointestinal stromal tumors

Imatinib mesylate, an oral tyrosine kinase inhibitor, is indicated for first-line treatment of patients with unresectable and/or metastatic gastrointestinal stromal tumors (GIST). Imatinib also is approved as adjuvant therapy for patients following resection of primary GIST. Despite the efficacy of imatinib for the treatment of patients with GIST, adherence to treatment can prove difficult.     

Response to imatinib mesylate of a gastrointestinal stromal tumor with very low expression of KIT

More than 90% of gastrointestinal stromal tumors (GISTs) express the receptor tyrosine kinase KIT, and activating mutations of the KIT gene are detectable in the vast majority of these tumors. Imatinib mesylate (formerly STI571) is a potent inhibitor of KIT kinase activity and has been proven to be highly active in patients with unresectable or metastatic GIST expressing immunohistochemically detectable KIT protein. Here we report a patient with metastatic GIST who responded well to imatinib mesylate treatment despite the near absence of KIT expression in two different samples of his tumor. The tumor was morphologically typical for a GIST, stained positively for CD34, and harbored an in-frame deletion (WK 557-558) in KIT exon 11 that is common in GISTs. Our experience with this patient suggests that even GISTs with very low levels of KIT expression may respond to imatinib mesylate therapy.     

Approval Summary: Imatinib Mesylate in the Adjuvant Treatment of Malignant Gastrointestinal Stromal Tumors

On December 19, 2008, the U.S. Food and Drug Administration approved imatinib mesylate tablets for oral use (Gleevec®; Novartis Pharmaceuticals Corporation, East Hanover, NJ) for the adjuvant treatment of adult patients following complete gross resection of Kit⁺ (CD117⁺) gastrointestinal stromal tumor (GIST). A randomized, double‐blind, placebo‐controlled study enrolling 713 patients was submitted. The primary objective of the clinical trial was to compare the recurrence‐free survival (RFS) intervals of the two groups. Overall survival (OS) was a secondary endpoint. Eligible patients were ≥18 years of age with a histological diagnosis of GIST (Kit⁺), resected tumor size ≥3 cm, and a complete gross resection within 14–70 days prior to registration. Imatinib, 400 mg orally, was administered once daily for 1 year. The study was terminated after completion of the third protocol‐specified interim analysis. At that time, 100 RFS events were confirmed by a blinded central independent review. With a median follow‐up of 14 months, 30 RFS events were observed in the imatinib group and 70 were observed in the placebo group (hazard ratio, 0.398; 95% confidence interval, 0.259–0.610; two‐sided p‐value < .0001). OS results are immature. Most patients in both groups experienced at least one adverse reaction, and 31% of the imatinib group and 18% of the placebo group experienced grade ≥3 adverse reactions. The most frequently reported adverse reactions (≥20%) were diarrhea, fatigue, nausea, edema, decreased hemoglobin, rash, vomiting, and abdominal pain. Drug was discontinued for adverse reactions in 17% and 3% of the imatinib and placebo‐treated patients, respectively.     

Tumeurs stromales du tube digestif (GIST)

Gastrointestinal stromal tumours (GIST) are rare malignant mesenchymal tumours caused by a functional mutation in c-kit or PDGF-A. Imatinib mesylate, a small molecule that targets KIT, PDGFR and ABL6BCR, has significantly changed the management and prognosis of these tumours. Although surgery remains the first-line treatment for localised GIST, patients respond to imatinib mesylate in 85 % of cases treated for metastatic disease, with a median time to progression of 2 years and a median survival of 5 years, compared with 12 months before imatinib treatment. The natural history of GIST and the outcome of imatinib mesylate treatment are strongly correlated with the tumour molecular characteristics, particularly its mutational status. A better understanding of the molecular processes will make it possible to optimise patient care, particularly with regard to determining the place of surgery in treating advanced disease, the role of imatinib exposure in the kinetics of emergent resistance, imatinib as an adjuvant treatment in high-risk, non-metastatic disease, and the future of newly available targeted molecules, such as sunitinib.