Application of sunitinib in the treatment of advanced gastrointestinal stromal tumor

Objective To investigate the efficacy of sunitinib in the treatment of patients with imatinib resistant 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 Bultrasound 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 (χ²=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 (χ²=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.