| BackgroundCancer pain brings great suffering to the terminally ill.Oxycodone hydrochloride sustained-release tablets as the first-line drug for the treatment of severe cancer pain,NCCN guidelines recommend that the initial titration dose is10 mg,but clinical practice has found that there are individual differences in the analgesic effects of different patients under this titration dose.Recent studies have shown that ABCB1 C3435 T and OPRM1 A118 G gene polymorphisms may play an important role in individual differences in opioid analgesia treatment.This study was intended to investigate the efficacy of 10 mg and 20 mg oxycodone hydrochloride sustained-release tablets in patients with severe cancer pain,and to study the effects of ABCB1 C3435 T and Oprm1 A118 G gene polymorphisms on the analgesic effect and the required amount of oxycodone hydrochloride sustained-release tablets.Objective1.This study aims to explore the efficacy of two different initial dose titration regimens of 10 mg and 20 mg Oxycodone Hydrochloride sustaine-releas-e tablets for patients with severe cancer pain,and to preliminarily define the effective and rapid titration regimens of Oxycodone Hydrochloridesustained-rele-ase tablets for patients with severe cancer pain.2.The effect of ABCB1 C3435 T and OPRM1 A118 G gene polymorphisms on the efficacy and the required dosage of Oxycodone Hydrochloride sustained release tablets in the treatment of severe cancer pain was preliminarily clarified,so as to provide a basis for the individualized treatment of cancer pain.Methods1.A total of 148 patients with severe cancer pain who were initially treated in the Clinical Cancer Center of our hospital from January 2019 to October 2020 and had not previously systematically used opioids were selected and randomly divided into the experimental group and the control group,74 patients in each group.Oxycodone hydrochloride sustained-release tablets were given orally according to the titration principle(dosage form:The starting dose of Bard Pharmaceuticals Limited was 10 mg q12h for the control group and 20 mg q12h for the experimental group.The analgesic effect and adverse reactions were evaluated after 1 hour of administration.When the pain broke out,the dose of relief medication needed was 10-20% in the background of 24 h.After the conversion of opioid dose,the patient was given oral ready-release morphine tablets(dosage form: 5mg/ tablet Qinghai Pharmaceutical Factory National Drug Approval(H20033010).24 h later,the total dose of opioids in the two groups was calculated,which was converted into the dose of Oxycodone Hydrochloride sustained-release tablets.For those whose 24 h comprehensive evaluation score was ≥7,the total dose in the first 24 h was increased by 1/2 to 1times;For those with a comprehensive score of 4-6,the total acting dose in the first 24 hours was increased by 1/4 to 1/2 times;For those with a comprehensive score of 0 ～ 3,the total amount of oral drugs needed in the first 24 hours was calculated for maintenance therapy.And so on until the dose titration reaches steady-state;The remission rates at 1h,12 h and 24 h in the experimental group and the control group were recorded.Completed titration within 3 days;NRS scores at 1h,12 h,24h,48 and 72h;Dosage and adverse reactions of Oxycodone Hydrochloride Sustained Release Tablets;2.Seventy-four patients in the first part of the experimental group were included in the second part of the study,and 30 patients with advanced severe cancer pain were further included.The titration regimen was the same as that in the first part of the experimental group.2 ml venous blood collecting on admission from extract DNA in serum,using Polymerase Chain Reaction(Polymerase Chain Reaction,PCR)technology of ABCB1 C3435 T and OPRM1A118 G genotyping,at the same time to 20 mg of oxycodone hydrochloride zyban as initial dose titration,titration method with the first part,the titration after stability,According to different alleles of ABCB1 C3435 T,they were divided into CC group(wild type homozygous genotype),CT group(heterozygous genotype)and TT group(mutant homozygous genotype).The amount of 24H-oxycodone hydrochloride continuous release tablets and adverse reactions of nausea,vomiting,constipation and dizziness in the three genotypes were recorded.In the same way,the amount of 24H-Oxycodone Hydrochloride sustained-release tablets in the AA group(wild type homozygous genotype),AG group(heterozygous genotype)and GG group(mutant homozygous genotype)as well as adverse reactions of nausea,vomiting,constipation and dizziness were recorded in ORM1 A118 G.In order to analyze the interaction between the two genes,they were further divided into 7 groups :CC + AA group,CC + AG group,CC + GG group,CT + AA group,CT + AG group,CT + GG group and TT group.Doses of 24 H-Oxycodone Hydrochloride sustained-release tablets and adverse reactions such as nausea,vomiting,constipation and dizziness were recorded in 7 groups.Results1.Inthe initial titration group of 1.20 mg Oxycodone Hydrochloride sustaine-release tablets,the 1-hour and 24-hour pain relief rate of patients was significantly higher than that of the conventional 10 mg initial titration group(P<0.05),and the 12-hour pain relief rate of patients in the experimental group was higher than that of the control group,but the difference was not statistically significant.In the experimental group,52 patients completed titration within 3days,accounting for 70.2%;in the control group,40 patients completed titration within 3 days,accounting for 54.0%.The difference was statistically significant by chi-square test.NRS scores of the experimental group at 1h,12 h,24h,48 and72 h were significantly lower than those of the control group(P<0.05).There was no significant difference in the consumption of 24h-Oxycodone hydrochloride sustained-release tablets between the two groups.2.The general data of ABCB1 C3435 T patients with CC type,CT type and TT type showed no difference.Compared with the CC/CT group,the 24h-oxy dosage in the TT group was lower,but the difference was not statistically significant.The weight-24h-oxy dosage and weight-body surface area-24h-oxy dosage in the CC,CT and TT groups were compared,and the differences were not statistically significant.3.There was no difference in the general data of OPRM1 A118 G group of AA,AG and GG patients,and the dosage of 24 h Oxycodone Hydrochloride sustained-release tablets in patients was significantly lower than that in the GG/AG group,with statistical difference(P < 0.05).The dosage of weight-24h-Oxycodone Hydrochloride sustained-release tablets and weight-body surface area-24h-Oxycodone Hydrochloride sustained-release tablets were compared among the three groups of AA,AG and GG.The results showed that the dosage of AA type was lower(P=0.036,P=0.031),and the difference was statistically significant.4.In order to analyze the interaction between ABCB1 and OPRM1 genes,since there were only 10 cases of TT type,I took TT(including TT+AA,TT+AG and TT+GG)as one group,so we divided them into 7 groups :CC+AA group(16 cases),CC+ AG group(23 cases),CC+GG group(5 cases),CT+AA group(10 cases),CT+AG group(26 cases),CT+ GG group(6 cases)and TT group(10cases).After titration,the results of this study showed that there was no statistical difference in the consumption of oxycodone hydrochloride between CC type and CT type groups.However,the consumption of 24h-Oxycodone Hydrochloride sustained-release tablets in CC+G type patients was significantly higher than that of CT+ Ag(P=0.006).The consumption of 24h-Oxycodone Hydrochloride sustained-release tablets in CC+GG type patients was significantly higher than that in CT+AA and TT type patients(P =0.001,P=0.009).ConclusionThis experiment confirmed that 20 mg oxycodone hydrochloride sustained-release tablets as the initial titration dose for severe cancer pain could improve the remission rate with good safety.OPRM1A118 G gene polymorphism has an effect on the requirement effect of oxycodone hydrochloride sustained-release tablets for severe cancer pain.The interaction of ABCB1C3435 T and OPRM1A118 G is related to the requirement of oxycodone hydrochloride sustained-release tablets for patients with severe cancer pain.Gene polymorphism may be one of the mechanisms for the difference in analgesic efficacy of oxycodone hydrochloride sustained-release tablets. |
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