Efficacy Of Double-Drug And Single-Drug Chemotherapy In Second-Line Treatment Of Advanced Gastric Cancer

Objective: To analyze the efficacy of double-or single-agent chemotherapy in patients with advanced gastric cancer in second-line treatment,and to analyze the predictive and prognostic factors affecting second-line treatment of advanced gastric cancer,and provide a theoretical basis for the clinical practice of second-line chemotherapy in patients with advanced gastric cancer.Methods: The present study used retrospective analysis.Medical records,laboratory tests,and imaging findings of patients who were diagnosed with advanced or metastatic gastric cancer in the department of medical oncology,the first hospital of China Medical University between June 1,2010 to June 1,2018 were cellected.Patients’ clinical characteristics,such as gender,age,pathological features,surgical conditions,the number and location of metastatic lesions,and other relevant clinical data,as well as survival information were recorded.Survival analysis was performed using Kaplan-Meier curve and Log-rank test to compare the efficacy of the two groups,using Cox Ratio Risk model for multivariate survival analysis to explore prognostic factors affecting second-line treatment in patients with advanced gastric cancer.Rresults: A total of 229 patients were enrolled in the study.According to the second-line chemotherapy regimen,they were defined as single-drug group with a total of 87 patients and double-drug group with 142 patients.The data showed that in the double-drug group more patients were ≤57 years old(58% vs.26%),no family history of cancer(81% vs.66%),and the primary tumor was located in the fundus and corpus(46% vs.25%).Other clinical facors between the two groups were balanced.In single-drug group,the proportion of patients receiving maintenance therapy in first-line treatment was higher than that in the double-drug group(24% vs.13%),and the difference was statistically significant(p=0.030).The proportion of patients receiving third-line therapy in the single-drug group was lower than that in the double-drug group(29% vs.44%),and the difference was statistically significant(p=0.026).For second-line treatment,the drugs used in the single-drug group include irinotecan(38%),fluorouracil(32%)and taxanes(28%).In the double-drugs group,fluorouracil(86%),taxanes(47%)and platinum(39%)were used.The major chemotherapy regimens include fluorouracil + taxane(45%)and fluorouracil + platinum(32%).Patients with second-line chemotherapy less than 4 cycles were 84% in the single-drug group and 86%in the double-drug group.Patients who were treated with targeted agent in second-line treatment were 36% in the single-drug group and 9% in the double-drug group.The difference was statistically significant.The objective response rates(ORR)for the the two groups were 9%.The disease control rate in the single-drug group was 34%,and was39% in the double-drug group.Survival analysis showed that the median progression free survival(PFS)time was 3.1 months for second line therapy in 229 patients with advanced gastric cancer.In single-drug group PFS was 2.3 months and in the double-drug group PFS was 3.3 months.The median overall survival(OS)was 5.9months.OS was 4.0 months in single-drug group and 6.5 months in double-drug group.The differences of OS or PFS between the two groups were not statistically significant.Subgroup analysis showed that in the patients with high-medium differentiation(HR3.943,95% CI 1.544-10.067,p=0.004),no surgical treatment(HR 2.444,95% CI1.412-4.229,p=0.001),baseline CA12-5>35u/ml(HR 1.809,95% CI 1.043-3.136,p=0.035),CA72-4≤6.9u/ml(HR 2.000,95% CI 1.127-3.548,p=0.018)and no response to the first line treatment(HR 2.685,95% CI 1.068-6.748,p=0.036),double-drug achieved significantly longer OS than single-drug.Multivariate analysis showed prior surgical treatment,progressing site in first-line treatment,granule-lymphocyte ratio and CA12-5 levels at baseline of second-line therapy were independent prognostic factors for second-line treatment in patients with advanced gastric cancer.Conclusion: For the second-line treatment of advanced gastric cancer,compared with single-drug chemotherapy,double-drug chemotherapy can not significantly improve the ORR and DCR,and it also can not prolong PFS and OS.Prior surgical treatment,progressing site in first-line treatment,granule-lymphocyte ratio and CA12-5 levels at baseline of second-line therapy were independent prognostic factors for second-line treatment in patients with advanced gastric cancer.