| Background:Malignant tumors seriously endanger people’s lives and health,and their morbidity and mortality are increasing globally.The treatment of malignant tumors involves many disciplines,and currently mainly includes surgery,medical treatment,radiation therapy,molecular targeted therapy,interventional therapy and traditional Chinese medicine.Among them,gastric cancer is the fifth most common malignant disease in the world and the third leading cause of cancer-related death.According to the World Health Organization(WHO),more than 40%of cases occur in China.Despite the continuous development of diagnostic and therapeutic techniques for malignant tumors,there is currently no satisfactory treatment for advanced gastric cancer,especially the lack of effective treatment options for standard third-line and second-line standard chemotherapy.In the past 20 years,targeted therapy has made great progress and more and more patients with malignant tumors have benefited clinically.Molecular targeted therapy is a treatment that directly inhibits the growth and migration of tumor cells by acting on specific targets by targeting cellular signaling and other biological pathways during tumorigenesis and progression.According to the mechanism of action of anti-tumor targeted drugs,they can be divided into two categories:small molecule compounds(mainly small molecule tyrosine kinase inhibitors)and macromolecular monoclonal antibodies.Apatinib is a small molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2(VEGFR-2)for advanced gastric adenocarcinoma that has undergone at least two systemic progressions or relapses after chemotherapy.Or patients with adenocarcinoma of the gastroesophageal junction.Its main mechanism of action is competitive binding to the intracellular tyrosine ATP binding site,highly selective inhibition of VEGFR-2 tyrosine kinase activity,blocking signaling after vascular endothelial growth factor(VEGF)binding,thereby inhibiting tumors Angiogenesis.Clinical trials of drugs have shown that apatinib has better safety and a lower incidence of serious side effects.The purpose of this study was to investigate the adverse effects of apatinib in the treatment of various types of malignancies,as well as the correlation between efficacy and adverse effects in the treatment of gastric cancer.Methods:This study collected the clinical data of patients with malignant tumors treated with apatinib from June 2015 to September 2016 in Shandong Provincial Hospital.A total of 272 cases were followed up for observation and statistical analysis.Inclusion criteria:solid malignant tumor confirmed by pathology;ECOG score PS ≤ 2 points;no obvious blood routine,abnormal liver and kidney function.Exclusion criteria:women during pregnancy and lactation;discontinued by themselves due to personal or economic reasons unrelated to treatment;lost to follow-up.The patient’s clinical data were collected by reviewing the medical record system and telephone follow-up.The collected information included gender,age,disease type,ECOG score,number of treatment lines,initial dose,administration time,type and degree of adverse reactions,and adverse reactions according to CTCAE 5.0.The criteria are graded.To analyze the relationship between adverse reactions and clinical features and clinical outcomes in patients with gastric cancer,and to explore the relationship between the occurrence of adverse reactions and progression-free survival(PFS).Statistical analysis was performed using SPSS 23.0 software.χ2 test was used for comparison between groups.Cox regression model was used for multivariate analysis.Kaplan-Meier method was used for survival analysis.The difference was statistically significant at P<0.05.Results:1.General information.Of the 272 patients taking apatinib,199 were male,73 were female,145 were ≤62 years old,and 127 were>62 years old.Among them,157 cases of gastric cancer,22 cases of liver cancer,21 cases of colorectal cancer,19 cases of lung cancer,13 cases of esophageal cancer,of which gastric cancer accounted for 57.72%.2.Adverse reactions.Of the 272 patients taking apatinib,68(25.0%)had no significant adverse reactions,and other patients had varying degrees of nausea,hand and foot skin reactions,elevated blood pressure,fatigue,vomiting,and diarrhea in 81 patients(29.8).%),64 cases(23.5%),59 cases(21.7%),44 cases(16.2%),29 cases(10.7%),23 cases(8.5%),and patients also had bleeding,allergic reactions in different parts.Dizziness,headache,hair loss,lethargy,joint pain,hoarseness,etc.The majority of patients had an adverse reaction rate of grade I-II,and all of them were relieved by drug intervention or reduction.Very few patients stopped taking the drug because they could not tolerate adverse reactions.There were 37 patients with grade III-IV adverse events with an incidence of 14.7%.The highest incidence of severe adverse reactions were hand-foot skin reactions,gastrointestinal bleeding,and elevated blood pressure,with 19(7.0%),8(2.9%),and 5(1.8%),respectively.Chi-square test analysis showed that the incidence of adverse reactions in gastric cancer patients was lower than that of other malignant tumors(P=0.013),and the incidence of adverse events was higher in patients receiving combination chemotherapy than in monotherapy(P=0.007).There was no significant correlation between gender,age,initial dose,number of treatment lines,and adverse events(P>0.05).Cox regression model analysis showed that the incidence of adverse events was 6.067 times higher in patients receiving monotherapy than in patients receiving monotherapy(P=0.016).The incidence of adverse events in other malignant tumor patients was 2.130 times higher than that in patients with gastric cancer(P=0.013).There was no significant correlation between age,gender,number of treatment lines,initial dose and adverse events.There was no significant difference in the incidence of adverse events associated with elevated blood pressure(P= 0.589)in patients with a history of hypertension and those without a history of hypertension.For the skin reaction of the hands and feet,the incidence of hand and foot skin reactions in the high-dose group was 6 times higher than that in the low-dose group.The incidence of hand-foot skin reactions in the third-line or higher-treatment group was 1.8 times higher than that in the second-line treatment group.The results were significantly different.(P=0.028).For gastrointestinal bleeding,there was no significant difference in the incidence of gastric cancer patients compared with other cancer patients(P = 0.781).For patients with fatigue and loss of appetite,the incidence was 2.8 times higher in patients with normal appetite,and the results were significantly different(P<0.001).For nausea,the incidence of patients in the advanced age group was 1.6 times that of the younger patients(P=0.015),and the incidence of nausea in patients with gastric cancer was 1.6 times that of other cancer patients(P=0.009).The incidence of vomiting in patients with gastric cancer was twice that of other cancer patients(P=0.037),and the incidence of vomiting in patients with chemotherapy was 2.2 times that of monotherapy(P=0.046).3.Correlation between the efficacy of gastric cancer patients and adverse reactions.A total of 157 patients with gastric cancer were excluded from the treatment of 35 cases due to adverse reactions,a total of 122 cases.There were 93 male patients(75.4%),20 female patients(24.6%),a median age of 62 years,65 patients(53.3%)in the ≤ 62 age group,and 57 patients(46.7%)>62 years old.There were 12 patients(9.8%)in the low-dose group,104 patients(85.2%)in the middle-dose group,and 6 patients(4.9%)in the high-dose group.Forty-four(36.1%)patients received only two systemic regimens,and 78(63.9%)received two or more regimens.There were 106 patients(86.9%)who received monotherapy and 16 patients(13.1%)who received chemotherapy.Kaplan-Meier survival analysis showed that the median PFS was 6 months in the hand-foot skin reaction group,and the median PFS was 70 days in the patients without hand-foot skin reaction.The survival rate of patients with hand-foot skin reaction was significantly higher than that without hand and foot.Patients with skin reactions showed significant differences(P<0.001).The median PFS was 6 months in the group with elevated blood pressure,and the median PFS was 70 days in the adverse reaction group.The survival rate of patients with elevated blood pressure was significantly higher than that of patients without adverse blood pressure.The results were significantly different(P = 0.007).There was no significant correlation between the occurrence and efficacy of other adverse events.Conclusions:As a targeted drug against angiogenesis,apatinib may have various adverse reactions,such as high blood pressure,hand and foot skin reactions,proteinuria,fatigue,nausea and vomiting,diarrhea are mostly mild adverse reactions that can be relieved by symptomatic treatment,and can be controlled by drug intervention or reduction,whether or not combined with chemotherapy,initial dose,number of treatment lines,gastric cancer or other malignant tumors.However,the age,high dose,combined chemotherapy,multi-line treatment may increase the incidence of adverse reactions such as hand and foot skin reaction,digestive tract reaction,hypertension,which should be closely observed and treated in time.It is worth noting that patients with hand and foot skin reactions and high blood pressure have good therapeutic effects,long-term survival without progress,and skin reactions in the hands and feet and elevated blood pressure may be indicators for predicting the efficacy of apatinib. |
PDF Full Text Request