| BackgroundGastric cancer is the fifth most common malignancy in the world.Its mortality ranks the third in the world,secondary only to lung cancer and liver cancer.China is one of the highest incidental areas in the world,and there are about 400,000 new cases of gastric cancer in China,which imposed a heavy burden on individuals,families and society.The early detection rate of gastric cancer is low,and the majority of the diagnosis is made when disease is unresectable with metastasis.Even the patients who have undergone radical surgeries are prone to recurrence and metastasis after surgery.The treatment of advanced gastric cancer is limited,so the median overall survival rate is only less than 1 year.Chemotherapy is the main treatment in the comprehensive therapy of advanced gastric cancer.Chemotherapy often uses combinations of two or three drugs of the following five classes of regimens,platinum,fluorouracil,taxane,anthracycline and irinotecan.So far,there is no standard chemotherapy regimen for advanced gastric cancer,and the evaluation of efficacy of different chemotherapy regimens varies.Therefore,it is of great significance to study the efficacy of different chemotherapy regimens for the first-line treatment of advanced gastric cancer.This study collected 340 patients with advanced gastric cancer undergoing first-line chemotherapy during the period from 2008 to 2017 at Qilu Hospital of Shandong University,and compared the short-term efficacy,long-term efficacy,and side-effects of different regimens to evaluate the pros and cons of the commonly used chemotherapy regimens and to explore the factors affecting the prognosis of advanced gastric cancer in order to guide the clinical decision.Objectives1.To compare the effects of different first-line chemotherapy regimens on objective response rate(ORR)and progression-free survival(PFS)in advanced gastric cancer.2.To compare the differences in adverse effects among different regimens of first-line chemotherapy.3.To explore the risk factors of the prognosis of advanced gastric cancer.MethodsIn this study,patients with advanced gastric cancer who underwent first-line chemotherapy in Qilu Hospital of Shandong University during the period of 2008.1.1-2017.12.31 were collected,and data were obtained through the institute medical system and telephone follow-up.The information collected includes name,sex,age,body surface area,ECOG score,size of lesion,depth of invasion,number of lymph node metastasis,status of distant metastasis,pathological type and staging,method of surgical treatment,adjuvant chemotherapy,number of treatment lines,number of chemotherapy,chemotherapy regimen,chemotherapy initiation time,chemotherapy end time,efficacy evaluation method,efficacy evaluation time,ORR,PFS,myelosuppression,and gastrointestinal reactions.Inclusion criteria:the pathology was gastric adenocarcinoma,mucinous adenocarcinoma,or signet-ring cell carcinoma;the diagnosis was advanced gastric cancer,recurrence after radical resection,or palliative surgery;and the first-line chemotherapy is completed at least twice and reviewed regularly.Exclusion criteria:a combination with other treatments during first-line chemotherapy;dual primary cancer patients;patients who have not completed twice chemotherapy or lost to follow-up.SPSS 22.0 software was used for statistical analysis.Chi-square test was used to compare the differences in categorical variables between the two groups.Kaplan-Meier and Log-rank tests were used to calculate survival rates and draw survival curves.COX regression model was used for prognostic factors.P<0.05 was recognized as statistical significance.Results1.Patient enrollment and baseline dataA total of 417 first-line patients with advanced gastric cancer were collected.According to the exclusion criteria,13 patients were excluded due to a combination of first-line chemotherapy with other treatments,15 were excluded due to dual primary tumors,and 49 patients were excluded due to incomplete chemotherapy or follow-up.A total of 340 patients were finally included for the following analysis.(1)Basic information:Among the 340 patients,68.8%were males and 31.2%were females.The median age is 58.The average body surface area is 1.69m2.37.4%of all patients underwent radical gastrectomy,15.9%underwent palliative surgery,and 46.7%received no surgery.88.2%were pathologically adenocarcinoma,4.4%were mucinous adenocarcinoma,and 7.4%were insignia cell carcinoma.The average cycles of the first-line chemotherapy were 5.When undergoing first-line chemotherapy,34.7%of patients had liver metastases,62.6%of patients had celiac lymph node or retroperitoneal lymph node metastasis,22.6%of patients had peritoneum or omentum metastases.(2)Chemotherapy efficacy:CR+PR+SD accounted for 32.3%;PD accounted for 56.2%;11.5%were unevaluable.The median progression-free survival(PFS)time was 154 days,and 73.5%of patients had a median PFS less than 154 days.(3)Adverse effects:Myelosuppression at grade 0-4 were 39.4%,29.4%,26.2%,4.7%,and 0.3%,respectively.0-4 degrees gastrointestinal adverse reactions were 40.6%,45%,11.2%,3.2%,0%.2.Efficacy study and prognostic factors analysis of different chemotherapy regimens2.1 Docetaxel-containing versus Docetaxel-free chemotherapy(1)Basic information:There was a significant difference in age distribution between the two groups(P<0.05),and there was no significant difference in other clinical characteristics(P>0.05).(2)Chemotherapy efficacy:There was no significant difference in short-term therapeutic effect(P>0.05).The median PFS were 151 days and 157 days,with no significant difference in the two groups(P>0.05).Median PFS in Docetaxel and Docetaxel-free regimens were 142 days and 136 days for patients with liver metastases at first-line chemotherapy,with no significant difference(P>0.05).There was no significant difference in PFS between the two groups of patients with celiac lymph nodes or retroperitoneal lymph node metastases(P>0.05).(3)Adverse effects:There was a significant difference in bone marrow suppression between the two groups(P<0.05),while there was no significant difference in gastrointestinal adverse reactions(P>0.05).(4)Prognostic factors analysis:Univariate analysis:The PFS for patients with first-line chemotherapy>5 was significantly longer than those with first-line chemotherapy≤5(HR = 0.191,P<0.05).Multifactor analysis:The factors including ages ≤58 years,number of first-line chemotherapy ≤ 5,pathologically mucinous adenocarcinoma or signet-ring cell carcinoma,liver metastasis during first-line chemotherapy,and celiac lymph nodes or retroperitoneal lymph node metastases during first-line chemotherapy,are all poor prognostic factors.2.2 Oxaliplatin-containing versus Oxaliplatin-free chemotherapy(1)Basic information:There was a significant difference in the total number of first-line chemotherapy,prior surgical treatment,celiac lymph nodes or retroperitoneal lymph node metastases during first-line chemotherapy(P<0.05).Thwer was no significant difference in other clinical features(P>0.05).(2)Chemotherapy efficacy:There was a significant difference in the short-term efficacy and median PFS(P<0.05).In patients with liver metastases and celiac lymph nodes or retroperitoneal lymph node metastases,there significant differences in the median PFS between the two groups(P<0.05).(3)Adverse reactions:There was no significant difference in the degree of myelosuppression and gastrointestinal adverse effecys between the two groups(P>0.05).(4)Prognostic factors analysis:Univariate analysis:The PFS for patients with first-line chemotherapy>5 was significantly longer than those with first-line chemotherapy≤5(HR=0.191,P<0.05).Patients with Oxaliplatin group had significantly longer PFS than those without Oxaliplatin(HR =0.651,P<0.05).Multifactor analysis:The factors including ages ^58 years,number of first-line chemotherapy ≤5,pathological type of mucinous adenocarcinoma or signet-ring cell carcinoma,liver metastasis during first-line chemotherapy,celiac lymph nodes or retroperitoneal lymph node metastases during first-line chemotherapy,and Oxaliplatin-free group,are poor prognostic factors.2.3 Doublet versus triplet chemotherapy(1)Basic information:There was a significant difference in the total number of first-line chemotherapy,prior surgical treatment,and peritoneum or omentum metastases during first-line chemotherapy(P<0.05).There was no significant difference in other clinical features(P>0.05).(2)Chemotherapy efficacy:There was no significant difference in the short-term efficacy and median PFS between the two groups(P>0.05).(3)Adverse reactions:There was no significant difference in myelosuppression and gastrointestinal adverse reactions between the two groups(P>0.05).(4)Prognostic factors analysis:Univariate analysis:The PFS for patients with first-line chemotherapy>5 was significantly longer than those with first-line chemotherapy ≤5(HR=0.189,P<0.05).Multifactor analysis:Factors including number of first-line chemotherapy ≤ 5,pathologically mucinous adenocarcinoma or signet-ring cell carcinoma,and liver metastasis and celiac lymph nodes or retroperitoneal lymph node metastases during first-line chemotherapy,are poor prognostic factors.2.4 Oxaliplatin-containing versus Cisplatin-containing chemotherapy(1)Basic information:There were significant differences in age,prior surgical treatment,and celiac lymph nodes or retroperitoneal lymph node metastases during first-line chemotherapy(P<0.05).No significant difference in other clinical features(P>0.05).(2)Chemotherapy efficacy:There were significant differences in the short-term efficacy and median PFS between the two groups(P<0.05).(3)Adverse effects:There was no significant difference in myelosuppression between the two groups(P>0.05).There was a significant difference in gastrointestinal adverse reactions(P<0.05).(4)Prognostic factors analysis:Univariate analysis:The PFS for patients with first-line chemotherapy>5 was significantly longer than those with first-line chemotherapy ≤ 5(HR=0.197,P<0.05).Patients with Oxaliplatin group had significantly longer PFS than those with Cisplatin group(HR=0.649,P<0.05).Multifactor analysis:The factors,including the number of first-line chemotherapy≤5,previous surgery is palliative or not,pathological type of mucinous adenocarcinoma or signet-ring cell carcinoma,liver metastasis and celiac lymph nodes or retroperitoneal lymph node metastases during first-line chemotherapy,are poor prognostic factors.2.5 Efficacy of other chemotherapy regimensCompared with commonly used chemotherapy regimen for gastric cancer,there was no significant difference in median PFS(P>0.05).Conclusion1.In the first-line chemotherapy regimens for advanced gastric cancer,the short-term efficacy and long-term efficacy of the regimen containing Oxaliplatin were significantly better than those without Oxaliplatin,and the safety was comparable.Subgroup analysis showed that patients with liver metastases,celiac lymph nodes,or retroperitoneal lymph node metastases have significantly prolonged PFS with Oxaliplatin-containing regimens.2.In the first-line chemotherapy regimens for advanced gastric cancer,the short-term efficacy and long-term efficacy of the regimens containing Oxaliplatin were significantly better than those containing Cisplatin,and the gastrointestinal adverse effects were significantly reduced.3.The PFS for Docetaxel-containing chemotherapy regimen was longer than the regimen without Docetaxel,but there was no significant difference.4.In all patients in this study,age,total number of first-line chemotherapy,pathological type,liver metastasis during first-line chemotherapy,and celiac lymph nodes or retroperitoneal lymph node metastases during first-line chemotherapy,were independent prognostic factors of PFS.5.The above conclusions need to be further verified by prospective randomized controlled studies. |
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