Effects of docetaxel for postoperative chemotherapy of advanced gastric cancer based on propensity score matching / 中华消化外科杂志

ABSTRACT

Objective:To investigate the effects of docetaxel for postoperative chemotherapy of advanced gastric cancer.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 311 patients with advanced gastric cancer who were admitted to Lanzhou University Second Hospital from January 2013 to December 2018 were collected. There were 224 males and 87 females, aged from 26 to 82 years, with a median age of 58 years. Of 311 patients, 204 cases undergoing chemotherapy with the FOLFOX regimen (oxaliplatin, calcium folinate, 5-fluorouracil) were allocated into the FOLFOX group, and 107 cases undergoing chemotherapy with the FLOT regimen (docetaxel, oxaliplatin, calcium folinate, 5-fluorouracil) were allocated into the FLOT group. Observation indicators (1) the propensity score matching conditions and comparison of general data between the two groups of patients after matching; (2) follow-up; (3) analysis of survival factors; (4) subgroup analysis; (5) adverse reactions. Follow-up was performed using a combination of outpatient examination, hospitalization review and telephone interview to detect situations of patients chemotherapy, postoperative survival, tumor recurrence and metastasis up to February 2019. The propensity score matching was realized using the nearest neighbor method with 1 1 ratio and caliper setting as 0.02. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability method. Rank data was analyzed using non parametric Rank sum test. The survival curve and rate were respectively drawn and calculated using the Kaplan-Meier method. The survival analysis was done using the Log-rank test. Univariate analysis and multivariate analysis were conducted using the COX regression model. Subgroup analysis was done using interaction test. Results:(1) The propensity score matching conditions and comparison of general data between the two groups of patients after matching 198 of 311 patients had successful matching, including 99 in each group. Cases with tumor differentiated as poorly differentiation or well differentiation, cases with CA19-9 <27 U/mL or ≥27 U/mL, cases with CA125 <35 U/mL or ≥35 U/mL before propensity score matching were 109, 95, 156, 48, 186, 18 in the FOLFOX group, and 42, 65, 93, 14, 104, 3 in the FLOT group, respectively, showing significant differences in the above indicators between the two groups ( χ2=5.649, 4.798, 4.039, P<0.05). After propensity score matching, the above indicators were 44, 55, 85, 14, 96, 3 in the FOLFOX group, and 42, 57, 85, 14, 96, 3 in the FLOT group, respectively, showing no significant difference in the above indicators between the two groups ( χ2=0.082, 0.000, 0.000, P>0.05). (2) Follow-up 198 patients of the two groups after matching were followed up for 2 to 69 months, with a median follow-up time of 38 months. During the follow-up, 92 cases survived without tumor, 2 cases underwent tumor recurrence or metastasis, and 104 cases died including 103 with tumor related death and 1 case with non-tumor related death. The courses of chemotherapy were 5.6±0.7 and 5.4±0.8 for the FOLFOX group and FLOT group, respectively, showing no significant difference between the two groups ( t=1.651, P>0.05). The 1, 3, and 5-year cumulative survival rates of patients were 72.2%, 31.5%, 27.7% and 83.2%, 42.8%, 38.2% for the FOLFOX group and FLOT group, respectively. The median overall survival time were 21 months and 34 months for the FOLFOX group and FLOT group, respectively, showing significant difference between the two groups ( χ2=4.473, P<0.05). (3) Analysis of survival factors results of univariate analysis showed that cases undergoing chemotherapy with the FLOT regimen, cases with tumor as diffuse type of Lauren classification, cases with tumor as mixed type of Lauren classification, cases with tumor differentiated as well differentiation, cases with tumor diameter≥5 cm, cases with CA19-9≥27 U/mL, cases with carcinoembryonic antigen (CEA)≥3.4 μg/L, cases with tumor as T4 stage of T staging, cases with tumor as N2 stage of N staging, cases with tumor as N3 stage of N staging, cases undergoing distal gastrectomy and cases undergoing total gastrectomy were related factors influencing postoperative survival of patients ( hazard ratio=0.659, 1.617, 1.798, 0.672, 1.726, 1.655, 1.942, 2.036, 2.536, 4.085, 1.810, 2.310, 95% confidence interval 0.444-0.978, 1.024-2.556, 1.105-2.926, 0.457-0.990, 1.159-2.569, 1.006-2.723, 1.295-2.912, 1.190-3.484, 1.409-4.564, 2.491-6.697, 1.020-3.211, 1.261-4.233, P<0.05). Results of multivariate analysis showed that cases undergoing chemotherapy with the FLOT regimen, cases with CEA≥3.4 μg/L, cases with tumor as N2 stage of N staging and cases with tumor as N3 stage of N staging were independent risk factors influencing postoperative survival of patients ( hazard ratio=0.622, 1.732, 2.217, 4.039, 95% confidence interval 0.418-0.926, 1.124-2.670, 1.200-4.097, 2.448-6.662, P<0.05). (4) Subgroup analysis: results of subgroup analysis showed that of the different subgroups using gender, age, tumor Lauren classification, tumor differentiation degree, tumor location, tumor diameter, tumor markers, tumor T staging, tumor N staging and surgical procedures as subgrouping index, the efficacy difference between the FLOT group and the FOLFOX group was the same (interaction P>0.05). (5) Adverse reactions the incidence of grade Ⅲ-Ⅳ adverse reactions of leukopenia, anemia, thrombocytopenia, nausea, vomiting and liver and kidney dysfunction were 11.1%(11/99), 2.0%(2/99), 3.0%(3/99), 12.1%(12/99), 4.0%(4/99), 1.0%(1/99) and 34.3%(34/99), 1.0%(1/99), 9.1%(9/99), 24.2%(24/99), 4.0%(4/99), 0 in the FOLFOX group and the FLOT group, respectively. There were significant differences of the incidence of leukopenia and nausea between the two groups ( χ2=15.213, 4.889, P<0.05). There was no significant difference of the incidence of thrombocytopenia between the two groups ( χ2=3.194, P>0.05) and there was no significant difference of the incidence of anemia, vomiting and liver and kidney dysfunction between the two groups ( P>0.05). There was no patient in the two group withdrawal from chemotherapy as no tolerance to toxic reactions. All patients were treated with glucocorticoids, proton pump inhibitors and serotonin receptor antagonists during chemotherapy. Patients undergoing leukopenia were treated with granulocyte stimulating factor. Conclusions:Compared with FOLFOX regimen, FLOT regimen which adds docetaxel significantly prolongs the postoperative median overall survival time of patients with advanced gastric cancer. However, FLOT regimen increases the incidence of grade Ⅲ-Ⅳ adverse reactions of leukopenia and nausea.