Clinical Analysis Of Low Dose Gemcitabine Combined With Oxaliplatin In The Adjuvant Treatment Of Patients With Muscle-invasive Bladder Urothelial Carcinoma

Objective:On a global scale,bladder cancer is one of the most common malignant tumors of the urinary system,the incidence of the disease is progressively increasing.According to the depth of cancer invasion,bladder cancer is divided into muscle invasive bladder cancer and non-muscle invasive bladder cancer,in which the standard treatment of muscle invasive bladder cancer is radical cystectomy.In recent years,some comprehensive treatment of bladder preservation has been carried out at home and abroad.Intravenous adjuvant chemotherapy is a common comprehensive treatment after partial cystectomy of bladder or transurethral resection of bladder tumor.The commonly used postoperative intravenous adjuvant chemotherapy currently is gemcitabine combined with cisplatin chemotherapy,which has been proved to be able to inhibit the progression or recurrence of the patients with muscle invasive bladder cancer.However,the majority of muscle invasive bladder cancer patients are advanced patients.Because of these patients'serious condition or the older age and more complications,gemcitabine,one of the chemotherapeutic drugs,often leads to severe complications such as myelosuppression,renal insufficiency,anemia.Besides,cisplatin can leads to more severe nephrotoxicity and ototoxicity.Thus,these patients are incapable of tolerating the chemotherapy regimen of standard dose.Oxaliplatin has been proved to be very effective for the chemotherapy of bladder cancer.The toxicity of single drug chemotherapy is not common.It is not found that the renal toxicity related cases have been reported in clinical application,and its potential ototoxicity is much lower than cisplatin.The therapeutic effect of gemcitabine combined with oxaliplatin chemotherapy on advanced bladder urothelial carcinoma or metastatic urothelial carcinoma has been studied both here and abroad,but there are few reports on the possible complications of this scheme.This project provides experimental basis and theoretical basis for the application of new adjuvant chemotherapy for patients with muscle invasive bladder cancer by comparing the therapeutic effect of the new chemotherapy scheme and traditional one.Method:A total of 55 patients with bladder urothelial carcinoma who were treated in the First Affiliated Hospital of Dalian Medical University were analyzed retrospectively from June 2012 to August 2017.These patients without metastasis underwent partial cystectomy or transurethral resection of bladder tumor and postoperative pathological diagnosis of bladder urothelial carcinoma at stage T₂.In addition,standard dose of gemcitabine and cisplatin?GC?chemotherapy or low dose of gemcitabine and oxaliplatin?GEMOX?was performed after the operation.The chemotherapy regimens were:GC gemcitabine 1000 mg/m² to do intravenous drip on day 1 and day 8,combined with cisplatin 75 mg/m² divided into the first three days to do intravenous drip;GEMOX gemcitabine 600 mg/m² to do intravenous drip on day 1 and day 8,combined oxaliplatin100 mg/m² on the second day to do intravenous drip;each chemotherapy cycle was 28days.The effect of chemotherapy was compared by measuring the size of the tumor,the rate of tumor recurrence and metastasis during the chemotherapy.The clinical benefit reaction was compared by the degree of myelosuppression,KPS scores,ZPS levels,body mass index and the side effects during chemotherapy.Results:A total of 257 cycles of chemotherapy were completed in 55 patients.There were2 tumor recurrences in GC regimen group and 4 in GEMOX regimen group respectively.The respective recurrence rate was 9.09%and 12.12%?P=0.896?.The 6 patients underwent chemotherapy because of recurrence of tumor.In group GEMOX,there was 1lung tumor metastasis case during chemotherapy.During the long-term follow-up after the end of chemotherapy period,each group had 5 tumor recurrences,the total recurrence rate was 31.82%and 27.27%respectively?P=0.716?.Besides,each group had 1 lung metastasis case,and group GC had 1 bone metastases case.There was no significant difference in disease-free survival between the two groups?P=0.772?.The median follow-up time was 17.17 months.Varying degrees of myelosuppression were the most common complication after chemotherapy.Respectively,the incidence of level 1 of myelosuppression was 20.00%and 25.75%?P=0.878?,level 2 was 22.22%and8.38%?P=0.002?,and level 3 was 4.44%and 0.60%?P=0.020?.The myelosuppression was reversible,which could be relieved after the symptomatic treatment.No chemotherapy related death cases were found.The two chemotherapy regimens mainly affect hemoglobin and white blood cell on the blood system,the GC group has a greater impact on white blood cell?P=0.035?and the GEMOX group has a greater impact on hemoglobin?P=0.043?.GEMOX group has less influence on renal function?P=0.001?.The effects of the two schemes on non-infectious fever after chemotherapy were similar?P=0.493?.GC group was superior to GEMOX group in hematuria,abnormal liver function and electrolyte disturbance after chemotherapy?P<0.05?.GEMOX regimen is superior to GC regimen in nausea and vomiting after chemotherapy?P<0.05?.The two regimens have similar results in improving the quality of life of patients after operation.Conclusion:1.The GEMOX regimen is similar to the GC regimen currently used in chemotherapy.It has similar curative effect in MIBC adjuvant therapy for T2 stage without distant metastasis;2.The GEMOX regimen is superior to the GC regimen in the myelosuppression after chemotherapy,the effect on renal function,postoperative nausea and vomiting;3.The GEMOX regimen needs strict control of indications,and patients who are suitable for this plan can be given chemotherapy,so as to achieve greater clinical benefits.