Multicenter Investigation On Opioids Use And A Systematic Review For Effects Of The OPRM1 A118G Polymorphism On Opioid Analgesia In Cancer Pain

?Background?WHO developed a three-step "ladder" for cancer pain relief in adults to guide cancer pain management in the late 1980 s.To further standardize the treatment of cancer pain in China,the National Health Commission of the People's Republic of China conducted Good Pain Management(GPM)project nationwide in 2011.The Department of Oncology in Xijing hospital started the GPM project in 2013.But how is the analgesics used in cancer pain in the real world? Whether the analgesic medication for patients with cancer pain conform with the guidelines for standardized treatment of cancer pain? We have little epidemiological survey data to draw a conclusion in China;and we also need research and data to verify whether GPM program had improved cancer pain treatment or rational drug use in cancer pain patients.Opioids are the most important and widely-used drugs for cancer pain management.However,there is significant interindividual variability in response to opioids in terms of analgesic effect.Several studies have investigated the association between the OPRM1A118 G polymorphism and opioid requirements in cancer pain patients;however,the results were inconsistent.Some studies indicate that the G-genotype carriers required higher opioid doses to achieve similar level of pain relief than the AA patients,while others showed that OPRM1 A118 G had no effects on opioid requirements.Therefore,it is necessary to conduct systematic review and meta-analysis to better understand the association between OPRM1 A118 G polymorphism and cancer pain treatment.? Aims ? 1.To survey the pharmacotherapy of cancer pain in the real world.2.To investigate the changes of pharmacotherapy in cancer pain before and after Good Pain Management(GPM)project.3.To analysis the interindividual variability of opioids analgesia effects in cancer pain and discuss the factors that influence the interindividual variability preliminarily.4.To examine the association between OPRM1 A118G(rs1799971)polymorphism and opioid analgesia by systematic review and meta-analysis.?Methods?1.Collect the whole clinical data and prescription information about the all opioids used for cancer pain in 3 level three class A hospitals in Shaanxi province(Xijing Hospital,Chang'an Hospital,Baoji People's Hospital).2.The consumption amounts of opioid analgesics in 2012(before the GPM)and 2016(4 years after the GPM)in Xijing Hospital were collected and analyzed.3.A systematic search of the literature dating to August 31,2017 was conducted using Pub Med,EMBase,Sinomed,the Cochrane Library databases,web of science,the clinical trials,CNKI,VIP,CMFD and CDFD.Studies were selected by exclusion criteria.The standardized mean difference(SMD)of required amounts of opioids between AA homozygotes and the G-allele was calculated.?Results?1.In the 3 hospitals,oral opioid preparations were the main drugs used for cancer pain treatment,supplemented with fentanyl patch.There are only a few injection preparations and little Dolantin used for cancer pain treatment.2.The amount of oral controlled release opioid drugs consumed by outpatients increased from 18% in 2012 to91% in 2016 in GPM department(Oncology),which is higher than 76% in non-GPM departments in 2016.The proportion of long course prescriptions in outpatients increased from 58% in 2012 to 79% in 2016 in GPM department(Oncology),which is higher than49% in non-GPM departments in 2016.The amount of oral controlled release strong opioid drugs consumed by inpatients also increased from 68% in 2012 to 90% in 2016 in GPM department(Oncology),which is higher than 62% in non-GPM departments in 2016.Besides,the GPM departments had no Dolantin consumption in cancer pain treatment.3.Patients with the same NRS score may need different opioids amounts,and the difference may be as large as 10 times.This difference may be affected by gender and age;NRS score is one of the important factors that influence the interindividual variability for opioid analgesia effects;Patients with severe pain need more opioids amounts than patients with moderate pain.4.Twelve studies including 2118 participants were included in our analysis.Five studies were conducted on Caucasian patients,and the others on Asian patients.The meta-analysis results indicated that G-allele carriers(AG+GG)of the OPRM1 A118 G polymorphism required higher opioid doses for pain management than those with the AA homozygotes(SMD =-0.3;95% confidence interval [CI],-0.45 to-0.15;P < 0.001).This difference was more significant in Asian patient group.The heterogeneity between the studies were acceptable and we did not find any significant statistical evidence of publication bias.?Conclusion?1.In terms of the type of medication,the treatment for cancer pain in these3 hospitals conformed with the guidelines for standardized treatment of cancer pain.2.After 4 years' implementing of the GPM project,the GPM department improved dramatically than other departments in cancer pain treatment.The GPM department is more active and rational in cancer pain management than non-GPM departments.The GPM project has a significant effect in promoting rational drug use in patients with cancer pain.3.In Xijing Hospital,the patients with same NRS score may need different opioids amounts,and the difference may be as large as 10 times.This difference may be affected by gender and age.NRS score is one of the important factors that influence the interindividual variability for opioid analgesia effects;Patients with severe pain need more opioids amounts than patients with moderate pain.4.Our research indicates that the OPRM1 A118 G polymorphism is associated with opioid analgesia effects in cancer pain patients;G allele(AG+GG)carriers of OPRM1 A118 G polymorphism required more opioid analgesia in cancer pain management than AA homozygotes patients.This phenomenon is more significant in Asian patients.