A Evaluation On The Efficacy And Safety Of Weekly Paclitaxel Plus Carboplatin As Neoadjuvant Chemotherapy For Stage Ⅲ Gastric Cancer

Surgery is the only possible cure for gastric cancer.How to improve the R0 resection rate of gastric cancer is the key to improve the prognosis.Given to the curative experience of chemotherapy for advanced gastric cancer,preoperative neo-adjuvant chemotherapy is also gradually used in gastric cancer of middle-late stage and achieved good effect.It has also been the consensus of experts,and wrote into a clinical guide.Neoadjuvant chemotherapy-surgery-adjuvant chemotherapy mode(CSC)has become a comprehensive treatment model to improve the R0 resection rate and prognosis of advanced gastric cancer.This treatment model is also a focus of current research.The gastric cancer chemotherapy drugs most widely used in nowadays are mainly platinum and fluorouracil.FOLFOX,XELOX and SOX are the standard chemotherapy regimen of gastric cancer,but their efficacy is still not satisfactory.In clinical practice,the author found weekly paclitaxel plus carboplatin(TP)regimen not only for breast cancer has obvious curative effect,but also has an excellent effect for gastric cancer.In addition to the allergic reaction,the weekly paclitaxel plus carboplatin regimens has a characteristic of low side effects,which is easily to tolerate to the patients.Therefore,if we use this scheme as a preoperative neoadjuvant chemotherapy regimen for gastric cancer,we can reduce the preoperative staging of gastric cancer and improve the R0 resection rate,so as to improve the prognosis of advanced gastric caner.After retrieval and access to documents,the author found domestic and international research report about the new adjuvant chemotherapy regimen for Ⅲ stage gastric cancer is very scarce.This study,combined with clinic tightly,and patients with stage Ⅲ gastric carcinoma is as the research object.The purpose is to evaluate the efficacy and safety of weekly paclitaxel plus carboplatin as neoadjuvant chemotherapy for stage Ⅲ gastric cancer.From January 2015 to December 2016,30 clinical defined patients with stage gastric cancer in Gastrointestinal Tumor Surgery ⅢDepartment of First Affiliated Hospital of Hebei North University were enrolled in this study.They were randomly divided into two groups: experimental group treated with weekly paclitaxel plus carboplatin neoadjuvant chemotherapy regimen(group TP,n=15),control group treated with oxaliplatin plus S-1 neoadjuvant chemotherapy regimen(group SOX,n=15).Collected into clinical data of patients,including gastro-scope,ultrasound gastro-scope,biopsy pathology,CT,abdominal ultrasound,contrast,routine blood test,hepatorenal function,tumor markers and so on.Group TP was treated with weekly TP regimen neoadjuvant chemotherapy-radical operative for gastric cancer(D2)-postoperative adjuvant chemotherapy.Paclitaxel was administered intravenously 80 mg.(㎡)-1 on day 1,while carboplatin(AUC=1.5)was administered intravenously on day 1.The treatment was repeated every 3 weeks,a total of 3 cycles(9 weeks).When neoadjuvant chemotherapy was completed and rest for 3 weeks,we had a operation.Group SOX was treated with SOX regimen neoadjuvant chemotherapy-radical operative for gastric cance(D2)-postoperative adjuvant chemotherapy.S-1 was administered orally 80 mg/times.(2 times/day)for 14 days,while oxaliplatin(130mg/㎡)was administered intravenously on day 1.The treatment was repeated every 3 weeks,a total of 3 cycles(9 weeks).When neoadjuvant chemotherapy was completed and rest for 3 weeks,we had a operation.Patients were reexamined and evaluated 1week before surgery.First we evaluated the efficacy.The main outcome measures:(1)the changes of clinical stage after neoadjuvant chemotherapy,and effective rate of neoadjuvant chemotherapy in two group were ananlyzed by statistical method.(2)R0 resection rate and lymph node positive rate were analyzed for all patients.(3)Imaging changes of primary tumor.(4)Morphological changes of pathology and changes of Ki-67.(5)Changes of tumor markers such as CEA,CA199 and CA724 after neoadjuvant chemotherapy.Secondly,we evaluated the safety of neoadjuvant chemotherapy.The main outcome measures:(1)Toxic side effects of neoadjuvant chemotherapy.(2)Operative mortality and postoperative complications.We contrasted the efficacy and safety between two groups to explore the best neoadjuvant chemotherapy regimen for stage Ⅲ gastric cancer patients.Result 1 The evaluation of the efficacy of neoadjuvant chemotherapy:(1)changes of clinical stage after neoadjuvant chemotherapy: The clinical staging before and after neoadjuvant chemotherapy and pathological staging of two groups were compared.The 15 patients in group TP were with pCR,1case(6.7%);PR,13 cases(86.7%);SD 1 case(0%);PD,0 case(0%).The overall response rate of neoadjuvant chemotherapy was 93.3% and disease control rate was 100%.The 15 patients in group SOX were with pCR,0 case(0%);PR,8 cases(53.3%);SD,6 cases(40.0%);PD,1 cases(6.7).The overall response rate of neoadjuvant chemotherapy was 53.3% and disease control rate was 93.3%.The effective rate of group TP was higher than that of group SOX,and the difference was statistically significant(P<0.05).The results show that weekly TP regimen as neoadjuvant chemotherapy is associated with higher efficacy than SOX regimen.(2)R0 resection rate and postoperative lymph node positive rate were compared.Two groups were treated with radical operation for gastric cancer after neoadjuvant chemotherapy.(1)R0 resection rate(86.7%)in group TP was significantly higher than in group SOX(46.7%),and the difference was statistically significant(P<0.05).It illustrates that weekly TP(Paclitaxel plus carboplatin)regimen can increase the rate of R0 resection of patients of stage Ⅲ gastric cancer.And the effect is better than the group SOX.(2)In group TP,the number of pathological lymph node metastasis was 2.47±4.39,and the number of lymph node metastasis in group SOX was 3.73±3.41.(3)The statistical analysis showed that there was no statistical difference between the two neoadjuvant chemotherapy regimens in the treatment of lymph node metastasis(P>0.05).(3)Imaging changes of primary tumor after neoadjuvant chemotherapy:(1)Gastroscope: compared with before the neoadjuvant chemotherapy,size of tumor were reduced,the ulcer was shallow,and the ulcer was healing.The morphology of the tumor was significantly improved.The morphology changes were similar in the two groups,but the improvement was more obvious in the group TP.(2)Ultrasound: compared with before the neoadjuvant chemotherapy,the tumor gastric wall,number of intumesced abdominal lymph node and infiltration depth significantly reduced.The morphology changes were similar in the two groups,but the improvement was more obvious in the group TP.(3)CT: the size of tumor,tumor gastric wall,and infiltration depth significantly reduced.The morphology changes were similar in the two groups,but the improvement was more obvious in the group TP.(4)Morphological changes of pathology and changes of Ki-67:(1)In group TP,there were 1 case who was not diagnosed with cancer by pathology(pCR).The majority of patients with cancer cell can be reduced.In group SOX,the tumor cells were reduced in some patients,and most patients did not change significantly.(2)Ki-67:Both in group TP and group SOX,the expression of Ki-67 after neoadjunvant chemotherapy was lower than that before chemotherapy,but the difference was not statistically significant(P>0.05).(5)Tumor markers such as CEA,CA199 and significantly reduced(P<0.05).After neoadjuvant chemotherapy,CEA level in group TP was significantly lower than that in group SOX,the difference was statistically significant(P<0.05).But the level of CA199 and CA725 was similar,the difference was not statistically significant(P>0.05).2 The evaluation of the safety of neoadjuvant chemotherapy:(1)Comparison of toxicities between two groups:(1)Toxicities in TP regimen were lipsotrichia,feeble and myelosuppressive.Grade 3 toxicities were nauseous(13.3%),neutropenia(6.7%).There were no grade 4 toxicities.All toxicities were relieved or disappeared after symptomatic treatment.(2)Toxicities in SOX regimen were vomiting,chromatosis,prepheral neurotoxicity and liver dysfunction.Grade 3 toxicities were nauseous(20.0%),vomiting(13.3%),liver dysfunction(13.3%),anemia(6.7%),thrombocytopenia(6.7%),anorexia(6.7%)and.There were no grade 4 toxicities.All toxicities were relieved or disappeared after symptomatic treatment.There were no chemotherapy related death cases.(2)Comparison of operative mortality and postoperative complications: There were no operative death in two groups.And there were no postoperative complications,such as bleeding,anastomotic leakage,ananstomotic stenosis,obstruction and others.The results showed that weekly TP regimen and SOX regimen did not increase the risk of surgery and the incidence of postoperative complcations,and the toxicities of TP is lower.Conclusion Compared with SOX regimen,weekly TP regimen as neoadjuvant chemotherapy for stage Ⅲ gastric cancer is associated with high efficacy.Weekly TP regimen can increase significantly rate of R0 resection.The toxicities of weekly TP regimen were lower,the patients were easy to tolerate,and the risk of operative mortality and postoperative complications were not increased.Weekly TP regimen is a safe neoadjuvant chemotherapy regimen.Weekly Paclitaxel plus Carboplatin as Neoadjuvant Chemotherapy can be used as a preferred neoadjuvant chemotherapy regimen for stage Ⅲ gastric cancer.