| Objective:To investigate the efficacy and safety of second-line treatment of sunitinib malate after the failure of first-line clinical treatment with imatinib mesylate in patients with advanced gastrointestinal stromal tumor,and to provide a reference for the comprehensive evaluation of clinical value of sunitinib malate.Methods:Retrospective analysis was performed on the clinical data of 37 patients with advanced gastrointestinal stromal tumor who were admitted to the third department of the fourth hospital of hebei medical university from January 1,2003 to December 31,2018 and failed to receive first-line treatment with imatinib mesylate.Each patient was treated with sunitinib malate at 37.5mg/d,orally regularly.Blood routine,electrolytes,liver and kidney functions and thyroid hormone levels were tested once a month.Results of adverse drug reactions were recorded and evaluated according to CTC AE standard 4.0.CT was reviewed every 3 months,and the results were evaluated according to Choi’s standard 4.0.Follow-up was conducted by outpatient review and telephone.Results: 1 General information: 1.1 Gender and age: there were 23 males and 14 females,and the ratio of male to female was 1.6:1.The average age was 53 years old.1.2 Primary sites of tumor: 7 cases in the stomach,22 cases in the small intestine,3 cases in the rectum,and 5 cases in the abdominal cavity.1.3 Primary tumor resection: 28 patients underwent surgical resection,and 9 patients did not undergo surgery.1.4 Pathological types: spindle cell type in 25 cases,epithelioid cell type in 7 cases,mixed type in 5 cases.There were 11 cases with the number of mitotic phase≤5(PCS /50HPF)and 26 cases with the number>5(PCS /50HPF).1.5 Immunohistochemistry: the expression rates of CD117,DOG1,CD34 and Ki67 were 100%,86.5%,83.8% and 86.5%,respectively.1.6 Gene mutation: there were 25 cases of C-kit exon 11 mutation,7 cases of C-kit exon 9 mutation,and 5 cases of PDGFRA exon 12 mutation.1.7 Recurrence risk classification: 8 cases were at medium risk and 20 cases were at high risk.1.8 Physical fitness score: ECOG: 1 score: 27 cases,2 scores: 10 cases;KPS: 90 points: 24 cases,60 ~ 80 points: 13 cases.2 First-line treatment of imatinib mesylate: 2.1 Initial treatment: 30 cases took 400mg/d dose and 7 cases took 600mg/d dose.Thirty-seven patients took the drug for a total of 1,351 months,with an average of 36.5 months per case.2.2 Progress: liver metastasis in 16 cases,abdominal metastasis in 12 cases,and tumor enlargement in 9 cases(no operation cases).2.3 Treatment after drug resistance:Twenty-seven patients were transferred to second-line treatment with sunitinib malate,and the other nine patients with C-kit exon 11 mutation were dosed to 600mg/d,which progressed again 4 to 6 months later,and one patient with C-kit exon 9 mutation was dosed to 800mg/d,which progressed again 12 months later.After both of them progressed,they were transferred to the second-line treatment of sunitinib malate.3 Second-line treatment of sunitinib malate: 3.1 Clinical efficacy: a total of 701 months were used in 37 cases,with an average of 18.9 months per case.CT evaluation: 0 cases of CR(0%),4 cases of PR(10.8%),17 cases of SD(45.9%),16 cases of PD(32.4%),10.8% of ORR and 56.8% of DCR.3.2 Adverse reactions: blood system: there were 19 cases of leukopenia and 16 cases of thrombocytopenia.Non-blood system: 22 cases of fatigue,21 cases of appetite loss,17 cases of liver and kidney function impairment,16 cases of hand-foot syndrome,12 cases of diarrhea,10 cases of hypertension,9 cases of skin rash,1 case of hypothyroidism.Most of the adverse reactions were grade 1 ~ 2,with less grade 3 ~ 4 and no grade 5 adverse reactions.4 Survival conditions: 4.1 Follow-up results: among the 37 patients,25 survived and 12 died.4.2 Results of PFS and OS: median PFS of first-line treatment with imatinib mesylate: 28 months;Median PFS in second-line treatment with sunitinib malate :15 months;Median OS:17.0 months.4.3 Relationship between gene mutation types and PFS of first-line treatment : the median PFS of C-kit 11,exon 9 and exon PDGFRA12 were 33 months,24 months and 19 months,respectively(P< 0.05).4.4 Relationship between recurrence risk and PFS of first-line treatment : the median PFS was 50.5 months and 27.5 months,respectively,in the patients with moderate risk and those with high risk(P < 0.05).4.5 Relationship between the condition of primary tumor resection and PFS of second-line treatment: the median PFS of the resected and unresected patients was 14 months and 15 months,respectively(P> 0.05).4.6 Relationship between the metastasis site and PFS of second-line treatment: liver metastasis was observed in 23 cases,abdominal metastasis in 14 cases,and the median PFS in the two groups was 18 months and 8.5 months,respectively(P< 0.05).4.7 Relationship between gene mutation type and PFS of second-line treatment : after treatment with sunitinib malate,the median PFS of C-kit 11,exon 9 and exon PDGFRA12 were 14 months,15 months and 15 months,respectively(P< 0.05).Conclusion:1.Patients with gastrointestinal stromal tumors were treated with imatinib mesylate after operation.Metastasis occurred earlier in high-risk patients.The common sites of metastasis were liver and abdominal cavity.2.In patients with C-kit 11 exon mutation,imatinib mesylate had better therapeutic effect and drug resistance appeared later.3.When patients with advanced gastrointestinal stromal tumors develop resistance to imatinib mesylate,some patients can increase the therapeutic dose to control the disease,but eventually progress will still occur.4.After second-line treatment for patients with advanced gastrointestinal stromal tumor,sunitinib malate can improve DCR and prolong PFS.5.In patients with advanced gastrointestinal stromal tumor treated with second-line treatment with unisonib malate,the PFS was longer in patients with liver metastasis alone,but the effect of primary tumor resection on PFS was not statistically significant.6.Among patients with advanced gastrointestinal stromal tumor treated with second-line trreatment of sunitinib malate,those with C-kit 9 exon mutation had longer PFS.7.Adverse reactions in the blood system during the second-line treatment of sunitinib malate were mainly caused by leukopenia and thrombocytopenia.Non-hematological adverse reactions were mainly anorexia and fatigue.Grade 1 ~ 2 were the main adverse reactions. |
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