A Clinical Study Of Celecoxib Combined With Chemotherapy Treatment On Gastric Cancer

The research is a clinical study of celecoxib combined with chemotherapy in the treatment of gastric cancer,including two parts:(1)to evaluate the efficacy and safety for postoperative patients of celecoxib combined with chemotherapy as first-line therapy of gastric cancer;(2)to evaluate the efficacy of celecoxib combined with chemotherapy for patients which lost operation opportunity and relapse after radical operation.Objective: To evaluate the efficacy and safety of celecoxib combined with chemotherapy in the treatment of gastric cancer.Methods: To establish a multi-center,randomized,controlled and open clinical study,240 patients of gastric cancer which underwent radical surgery were research objects.120 patients were arranged as experimental group and the other 120 ones were control group.Another included 200 patients which metastatic or postoperative relapse of advanced gastric cancer were divided into the experimental group and control group with 100 cases respectively.All patients were performed strict inclusion and exclusion criteria.The shedding/termination criterion were established in the study.The experimental group was given celecoxib combined with chemotherapy,and the control group got the chemotherapy treatment only.Chemotherapy drugs were Fluorouracil(5-Fu,capecitabine,S-1,tegafur)and oxaliplatin in this study.To compare with chemotherapy treatment only,the efficacy and safety of celecoxib combined with chemotherapy treatment were evaluated in this study.Disease free survival(DFS),progression free survival(PFS)were used as the primary curative indicators,the objective response rate(RR),overall survival(OS)and quality of life(QOL)were the secondary curative indicators.And vital signs,laboratory indicators,adverse events(AE)and serious adverse events(SAE)were the primary safety indicators.We used ? = 0.05,? = 0.10 as the test level.The chi-square test was applied on various rates,and variance analysis on measurement data,Log-rank test and K-M analysis on survival data.Results:1.Demographic and baseline characteristics:In the part one of this study,three patients in the experimental group and seven in the control group withdrew from the study before receiving the assigned treatments.As a result,230 randomly assigned patients after radical operation of gastric cancer were included in the study,with 117 assigned to the experimental group and 113 assigned to the control group: 155 males and 75 females,aged from 31-70 years old,187 cases with ECOG score 0-1 points and 43 cases with 2 points.63 cases located in the stomach and esophagus of the primary tumor and 167 cases located in the body of the stomach.Proximal gastrectomy was performed in 41 cases,distal gastrectomy performed in 123 cases and total gastrectomy performed in 66 cases.D1 radical style was performed in 54 cases and D2 radical style in 176 cases.The tumor stages were40,125,65 cases in grade Ib,II and ? respectively.Histological classification included 138 cases of tubular adenocarcinoma,57 cases of mucinous adenocarcinoma and the 35 cases of ring cell carcinoma.Lauren classification included intestinal type in 138 cases,diffuse type in 39 cases,and mixed type in 53 cases.There were 115 cases with COX-2 positive and 107 cases with COX-2 negative.56 cases test sample of COX-2 were from the gastroscope and 166 cases from surgical operation.All patients performed strict inclusion criteria and exclusion criteria.There was no significant difference between the experimental group and control group about demographic and baseline characteristics.In the part two of this study,eleven patients in the experimental group and thirteen in the control group withdrew from the study before receiving the assigned treatments.As a result,176 randomly assigned patients with advanced gastric cancer were included in the study,with 89 assigned to the experimental group and 87 assigned to the control group: 130 males and 46 females,aged from 28-70 years old,133 cases with ECOG score 0-1 points and 43 cases with 2 points;92 cases in advanced and 84 cases in metastasis.Boundary could be measured in 78 cases and 98 cases can not be measured.108 cases were tubular adenocarcinoma,43 cases were mucinous adenocarcinoma,and 25 cases were ring cell carcinoma by histological type.Lauren type had 90 cases with intestinal type,42 cases with diffuse type,and 44 cases with mixed type.There are 102 cases with COX-2 positive and 72 cases with COX-2negative.86 cases test sample of COX-2 were from the gastroscope,66 cases form surgical operation,and 22 cases from metastasis foci.All patients performed strictinclusion criteria and exclusion criteria.There was no significant difference between the experimental group and control group about demographic and baseline characteristics.2.Results of celecoxib combined with chemotherapy treatment on the patients of post radical operation of gastric cancer: compared with the control group,the 3-year survival rate of the experimental group was 72%,and the control group was 68%.There was no significant difference found in two groups(P = 0.67).The 3-year disease free survival rate in experimental group was 64%,and the control group was51%(P = 0.41).In COX-2 positive subgroup,the 3-year survival rate of the experimental group was 78%,the control group was 66%,and the obvious statistic significance were reached(P = 0.02).In this subgroup,the 3-year disease free survival rate in experimental group was 70%,the control group was 50%,the big difference was found between the two groups(P = 0.01).3.Results of celecoxib combined with chemotherapy treatment on patients with advanced gastric cancer:in the short-term effects,the total effective rate and disease control rate in experimental group were 39% and 66% respectively.The total effective rate and disease control rate in control group were 30% and 54% respectively.And there was a significant difference between the two groups(P < 0.05).Overall survival of experimental group and control group were 12 months and 10 months respectively,and there was no significant difference(P = 0.59).In COX-2 positive subgroup,overall survival in experimental group and control group were 14 months and 10 months respectively,and the statistic difference was reached between the two groups(P = 0.01).The progression-free survival of experimental group and control group were 6 months and 5 months respectively,and no significant difference was found between the two groups(P = 0.73).In COX-2 positive subgroup,progression-free survival of experimental group and control group were 7.5 months and 5 months respectively,and there was a statistic difference between the two groups(P = 0.00).4.Safety evaluation of celecoxib combined with chemotherapy treatment on the gastric cancer: there was no significant difference between the celecoxib combined with chemotherapy group and chemotherapy alone group in drug-related side effects,including nausea,neutropenia,poor appetite,peripheral nerve toxicity,diarrhea,vomiting,fatigue,and thrombocytopenia.5.The quality of life assessment of celecoxib combined with chemotherapy teatment on the gastric cancer: the score of overall health status in experimental groupwas better than in control group by EORTC QLQ-C30 scale(P < 0.05).In the aspect of functional field,such as role,society,body,emotions and cognition,no significant difference was found between the experimental group and control group.However,in the aspect of symptoms,especially pain,fatigue,the experimental group was better than the control group(P < 0.05).The pain score in celecoxib combined with chemotherapy group was lower than in chemotherapy alone group(P < 0.05)by EORTC QLQ-STO22 scale.But there is no significant difference between two groups about limited diet,dysphagia,anxiety,reflux,taste,xerostomia,alopecia and somatotype.Conclusion: Celecoxib combined chemotherapy treatement on gastric cancer patients with COX-2 positive expression could make more benefits,including higher survival,disease free survival,progression free survival,quality of life and short-term curative effect,than chemotherapy treatment only without more side effects.