The Study Of Current Situation Of Imatinib Therapy In Gastrointestinal Stromal Tumor Patients

Objective:To investigate the clinicopathologic characteristics of gastrointestinal stromal tumors (GISTs) and understand the GIST patients’medication status and compliance. And to evaluate the efficacy and toxicity of imatinib mesylate in the treatment of recurrent/metastatic/unresectable GISTs or as post-operative/preoperative adjuvant therapy.Method:Ninety-one patients with GISTs were confirmed by pathologic and immunohistological examination from October2006to December2011. All patients were administered imatinib400mg/d. Fifty-three patients were classified to post-operative adjuvant group. Thirty-two patients were recurrent/metastatic/uresectable group. Six patients were preoperative adjuvant group. Regular follow-up was done to understand the medication and to evaluate the efficacy and adverse effects.Result:①Clinical and pathological features:Among the91patients there were49males and42females. Their age ranging between29-76years, the mean age of patients was54.8years, the median age was56years. Tumors located in stomach in43cases (47.2%), duodenum in7cases (7.7%), jejunum and ileum in30cases (33.0%), colorectum in6cases (6.6%), retroperitoneal in3cases (3.3%), other in2cases (2.2%). CD117positive rate was96.7%(88/91). DOG-1positive rate was100%(25/25). CD34positive rate was61.5%(56/91). SMA positive rate was15.4%(12/78). S-100positive rate was6.3%(5/80).②Medication situation:The average treatment time of19intermediate risk patients is9.7months. The average treatment time of34 high risk patients is18.5months. The average treatment time of32recurrent/metastatic/uresectable patients is25.0months. The average treatment time of6preoperative patients is20.3months.51patients used to interrupt the imatinib therapy, including14patients who ended their adjuvant therapy,3cases turning to sunitinib therapy,7died, and27cases of self-withdrawal. These self-withdrawals are due to economic reasons (14cases), adverse reactions (10cases) and tumor progression (3cases). The dose of imtinib therapy increased to600mg/d in3patients, reduced to300mg/d in1patient.4patients switched to sunitinib therapy.③Efficacy evaluation: All91patients were followed-up.53patients were treated as post-operative adjuvant therapy. With a median follow-up of22months,7patients were found recurrence.1year and2year recurrence-free survival rates (PFS) were88.5%and83.9%. Including19cases of intermediate risk patients,34cases of high-risk patients, recurrence rate and RFS between these two groups showed no significant difference (p>0.05). There were35patients still taking drugs at the last follow-up, while the other18patients interrupted their treatment for various reasons. The RFS and recurrence rate between these two groups were significantly different (p<0.05). In the32cases of recurrent/metastatic/uresectable patients,27patients were treated with imtinib only. With a median follow-up of20months,3patients were evaluated complete response CR(11.1%),5patients were evaluated partial response PR(18.5%),10patients were evaluated stabilization of disease SD(37.1%),9patients were evaluated progression of disease PD(33.3%),18patients (66.7%) were acquired clinical benefit (disease control).1year and2year progression-free survival (PFS) rates were70.7%and38.1%.1year and2year overall survival (OS) rates were95.7%and69.8%. The median progression time was20months.5patients were treated with imtinib after surgical resection of recurrent/metastatic lesions, including4cases of radical resection. With a median follow-up of9months, all4patients were free of recurrence or metastasis. Leaving1patient with palliative operation, he died after1year of medication therapy.6patients were treated as preoperative therapy. Successful resections were conducted in2patients after imatinib administration for10and12 months.1patient was waiting for surgery after8months of drug treatment.1patient was dead.2patients continued medication administration. With an average time of22months, both were evaluated PR.④Adverse effects:Adverse effects in most cases were mild and could be tolerated in one or two months. A small number of severe cases required reduction or withdrawal of imatinb.Conclution:①The diagnosis of GIST relies on histopathology and immunohistochemistry. The positive expression rates of CD117and DOG-1are high. So they can be used as the most important immunohistochemical indicators in the diagnosis of GIST.②Imatinib mesylate is effective in the treatment of metastatic/recurrent/unresectable GISTs or as post-operative/preoperative adjuvant therapy. And the adverse effects of imatinib are mild.③The main reasons of the poor compliance in GIST patients include economic reasons, imatinib resistance and adverse reactions. Stopping taking medicine of GIST patients voluntarily affects imatinib efficacy significantly. So the management and health education of GIST is essential.④In view of the role of gene mutations in the pathogenesis, drug efficacy and mechanisms of resistance in GIST, in the future, standardizing the handing of the pathological specimens is very important. To strengthen the gene mutation detection of GIST patients can achieve a better efficacy.