Clinical Study Of Cinobufotalin Combined With Opioids In The Treatment Of Cancer Pain In Patients With Opioid Tolerance

Objectives: To observe the effect of cinobufotalin combined with opioids on cancer pain,quality of life and symptoms in patients with opioid tolerance,and to evaluate adverse reactions.Methods: Using randomized and controlled methods,Patients with opioid intolerance who met the criteria for analgesia incompleteness were randomly divided into experimental group and control group.On the basis of the existing opioid analgesia schemes,the experimental group was treated with 0.5g po tid of cinobufotalin capsule,while the control group was treated with opioids only.The dosage of opioids was titrated dynamically according to pain in both groups for a total of 6 days.General information,changes in pain intensity,number of outbreaks of pain,changes in dosage of long-acting opioids,quality of life and symptoms were recorded.NRS score was used to assess pain intensity,OME was converted to oral dose,and EORTC QLQ-C30 was used to assess quality of life and health status.Evaluation Indicators:The main endpoint was PID,the secondary endpoint was BTP,and the other indicators were LOIR,quality of life and symptom assessment.ITT analysis was used to obtain data from the follow-up of dropped cases.The lost data were processed by LOCF method.Results: After treatment,the pain intensity score of the two groups decreased compared with that before treatment,and the difference was statistically significant(P< 0.05).There was no significant difference in NRS score between the two groups after 3 days and 6 days of treatment(P > 0.05),and there was no significant difference in PID score between the two groups(P > 0.05).The frequency of BTP in the two groups decreased after 1-3 days of treatment,but there was no significant difference between the two groups(P > 0.05).The frequency of BTP in the experimental group was lower than that in the control group after 4-6 days of treatment,with statistical significance(P < 0.05).After 6 days of treatment,the increase rate of LOCF in the experimental group was lower than that in the control group,with statistical significance(P < 0.05).After treatment,the sleep,mood and quality of life of the experimental group were improved compared with those before treatment,with statistical significance(P < 0.05),and there was no statistical significance between fatigue and appetite before treatment(P > 0.05);after treatment,the quality of life ofthe control group was improved compared with that before treatment,with statistical significance(P < 0.05),and there was no statistical difference between sleep,fatigue,appetite and mood before treatment.Significance(P > 0.05);after treatment,the sleep and mood improvement of the experimental group was better than that of the control group,with statistical significance(P < 0.05).Adverse reactions: There were different degrees of constipation in the experimental group and the control group,and the proportion of constipation in the experimental group(69.6%)was less than that in the control group(90.9%);the other adverse reactions in the experimental group were mainly nausea,dizziness,abdominal distention and diarrhea,while the adverse reactions in the control group were nausea,dizziness,abdominal distention,sleepiness,itching of skin and urinary retention.Both groups had cases falling out.The high rate of falling out in the control group(18.1%)was related to adverse reactions.Conclusions: Intervention with cinobufotalin and opioids in patients with opium intolerance with incomplete analgesia can reduce outbreak pain,reduce the increase of opium,improve sleep and mood,and improve the quality of life.It has less adverse reactions and safety.The role of combination therapy in pain management of opioid tolerance should be further emphasized and studied.