| BackgroundChemotherapy is one of the important methods for the treatment of malignant tumors,and chemotherapy-induced nausea and vomiting(chemotherapy-induced nausea and vomiting,CINV)is one of the most common adverse reactions in patients,and it is also an important reason for many tumor patients to fear chemotherapy.CINV will not only bring discomfort to patients and affect their quality of life(quality of life,QOL),but also reduce their compliance,thus delaying or terminating anti-tumor therapy.Therefore,reasonable and effective control of CINV occupies a very important position in the comprehensive treatment of tumors.Chemotherapy with cisplatin is a commonly used first-line chemotherapy regimen in clinic,and it is also considered as highly emetogenic chemotherapy(highly emetogenic chemotherapy,HEC).If prophylactic antiemetic drugs are not provided,more than 90%of patients will develop nausea and vomiting.For patients receiving highly emetogenic chemotherapy,acute CINV can be prevented by first-generation 5-hydroxytryptamine 3 receptor antagonists such as ondansetron or granisetron in combination with dexamethasone.Compared with the first-generation 5-HT3 receptor antagonist,the long-acting second-generation 5-HT3 receptor antagonist palonosetron can more effectively prevent delayed CINV,induced by HEC,but the results are still not satisfactory.In recent decades,the emergence of NK-1(neurokinin-1,NK-1)receptor antagonists and olanzapine have improved the prevention of delayed CINV.The current multinational guidelines all recommend the use of a triple antiemetic regimen consisting of NK-1 receptor antagonist,5-HT3 receptor antagonist and dexamethasone to prevent CINV induced by highly emetogenic chemotherapy.However,a number of studies have shown that the proportion of patients who use this regimen to achieve complete remission(that is,no vomiting and no rescue treatment)is only about 50%,while about 70%of patients are still not fully controlled during the delayed period.In China,because the price of NK-1 receptor antagonist is high and it is not a medical insurance reimbursement drug,so the scope of use is very limited.At the beginning of this study,the scheme has not been widely used in our country.At present,the most commonly used clinical antiemetic regimen in China is still 5-HT3 receptor antagonist combined with dexamethasone,and the preventive effect on delayed CINV is not good.Therefore,how to effectively prevent and reduce delayed CINV caused by HEC is still a prominent problem to be solved in clinical practice.Megestrol is a kind of artificial semisynthetic progesterone with good oral absorption effect and no obvious adverse reactions.it is widely used in clinical treatment of uterine cancer,breast cancer and prostate cancer which are strongly dependent on hormone.In the clinical application of megestrol,it is also found that megestrol can effectively reduce digestive tract reaction and myelosuppression,and increase the appetite and body weight of tumor patients.At present,megestrol acetate dispersible tablets have been widely used in tumor patients to increase appetite,improve cachexia syndrome and improve chemotherapy tolerance and quality of life.In this study,patients who received hyperemetic chemotherapy regimen containing cisplatin were randomly divided into two groups:one group adopted the standard two-combination antiemetic regimen of 5-HT3 receptor antagonist combined with dexamethasone,and the other group adopted a triple antiemetic regimen consisting of megestrol acetate dispersible tablets on the basis of two-combination antiemetic regimen.The inhibitory effects of the two regimens on digestive tract reactions in patients treated with hyperemetic chemotherapy were compared.To investigate the clinical efficacy and safety of megestrol acetate dispersible tablets combined with 5-HT3 receptor antagonist and dexamethasone in the treatment of CINV,especially delayed CINV.ObjectivesTo compare the efficacy and safety of megestrol acetate dispersible tablets combined with 5-HT3 receptor antagonist and dexamethasone triple antiemetic regimen and 5-HT3 receptor antagonist and dexamethasone combined antiemetic regimen in the control of CINV induced by hyperemetic chemotherapy.Materials and Methods120 patients with malignant tumors diagnosed by pathology or cytology and treated with highly emetogenic chemotherapy drugs containing cisplatin from September 2018 to December 2019 were selected.The patients were randomly assigned to megestrol group(megestrol acetate dispersible tablets+5-HT3 receptor antagonist+dexamethasone)or control group(5-HT3 receptor antagonist+dexamethasone)at 1:1.The dosage of antiemetic drugs in the control group:Palonosetron 2.5mg,dexamethasone 12mg on the first day,8mg on the 2nd-4th day,all were injected intravenously with 30min before chemotherapy for 5 days.The patients in the megestrol acetate group were given megestrol acetate dispersible tablets on the basis of the control group.160 mg of megestrol acetate dispersible tablets were taken orally every morning on the day of the beginning of chemotherapy for 10 days.The main end point was the proportion of control of nausea and vomiting between the two groups during the delayed period(24-120 hours after the beginning of chemotherapy),that is,the proportion of complete remission(no vomiting and no need for rescue treatment)and complete prevention(no nausea and vomiting).The secondary end point was the control ratio of nausea and vomiting in the acute phase(0-24 hours after the beginning of chemotherapy)and the overall phase(0-120 hours after the beginning of chemotherapy);the proportion of patients with grade 3-4 nausea and vomiting during chemotherapy;the adverse reactions related to antiemetic drugs and the score of quality of life of patients in both groups before and after treatment.Results1.Comparison of basic data between two groups of patients:A total of 120 patients were randomly assigned to the megestrol group and the control group,with 60 patients each.All patients successfully completed 1-2 cycles of chemotherapy.There were no statistical differences in clinical data such as age,gender,tumor type,and physical status score between the two groups of patients,and they were comparable.2.Comparison of the control of nausea between the two groups of antiemetic regimens in different periods:For the control of nausea,during the delayed observation period,the proportion of complete prevention between the megestrol group and the control group was 53.3%(31/60)and 30.0%(18/60),respectively,and there was significant difference between the two groups(P=0.012).During the overall observation period,the rates of complete prevention between the megestrol group and the control group were 40.0%(24/60)and 15.0%(9/60),respectively,and there was significant difference between the two groups(P=0.002).In the acute observation period,the percentage of complete prevention between the megestrol group and the control group was 70.0%(42/60)and 65.0%(39/60),respectively,and there was no significant difference between the two groups(P=0.559).The results showed that the control rate of nausea in the megestrol group was significantly higher than that in the control group in both the delayed phase and the overall phase;in the delayed phase,more than 50%of the patients in the megestrol group achieved complete prevention.3.Comparison of the control of vomiting between the two groups of antiemetic regimens in different periods:For the control of vomiting,during the delayed observation period,the proportion of complete remission between the megestrol group and the control group was 76.7%(46/60)and 51.7%(31/60),respectively,and there was significant difference between the two groups(P=0.001).During the overall observation period,the rates of complete remission between the megestrol group and the control group were 68.3%(41/60)and 46.6%(28/60),respectively,and there was significant difference between the two groups(P=0.016).In the acute observation period,the percentage of complete remission between the megestrol group and the control group was 81.7%(49/60)and 78.3%(47/60),respectively,and there was no significant difference between the two groups(P=0.648).The results showed that the control rate of vomiting in the medroxyprogesterone group was significantly higher than that in the control group in both the delayed phase and the overall phase;in the delayed period,the vomiting control rate in the megestrol group was 25%higher than that in the control group.4.Comparison of adverse reactions between the two groups of patients:the adverse reactions related to antiemetic drugs in the two groups mainly included fatigue,constipation and hiccups.Among them,the incidence of fatigue in megestrol group and control group was 11.7%(7/60)and 3%(5/60)respectively,the incidence of constipation was 18.3%(11/60)and 8.3%(5/60)respectively,and the incidence of hiccup was 1%(1/60)and 3.3%(2/60)respectively,there was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).5.Comparison of the quality of life between the two groups:the quality of life(QOL)of cancer patients in China was used to compare the quality of life of the two groups of patients before and after treatment.There was no statistical difference in QOL scores between the two groups of patients before treatment(P>0.05),but the QOL scores of patients in the megestrol group were higher than those in the control group after treatment,and the difference was statistically significant(P<0.05).Conclusion1.On the basis of the combined antiemetic regimen of 5-HT3 receptor antagonist combined with dexamethasone,the addition of megestrol acetate can significantly improve the CINV caused by highly emetogenic chemotherapy regimen containing cisplatin,especially in the prevention of delayed CINV without aggravating the adverse reactions.2.The triple antiemetic regimen of megestrol combined with 5-HT3 receptor antagonist and dexamethasone can not only control CINV caused by highly emetogenic chemotherapy regimen,but also increase appetite,improve patients’quality of life,and improve patients’ compliance and tolerance to chemotherapy,which has a very positive effect on patients treated with cisplatin and other highly emetogenic chemotherapy drugs. |
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