OBJECTIVETo investigate the efficacy and safety of sunitinib on the management of gastrointestinal stromal tumors (GIST) patients with imatinib resistance.

METHODSClinical 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).

RESULTSThe 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 35 weeks 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 157 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).

CONCLUSIONSSunitinib 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 protocol of sunitinib 37.5 mg/d CDD possesses better safety.