便秘通对癌症患者阿片类药物相关便秘的疗效及安全性研究

Efficacy and Safety of "Bianmitong" on Opioid-induced Constipation in Cancer Patients

背景使用阿片类药物治疗中重度癌痛患者常常出现阿片类药物相关性便秘(OIC),OIC可导致许多患者被迫减少或停止阿片类药物的使用,癌症患者OIC的治疗至关重要。目的采用临床随机对照和延伸研究评估便秘通对癌症患者OIC的疗效和安全性。方法以2017年1月-2018年2月西南医科大学附属中医医院肿瘤科129例OIC患者为研究对象,使用中央随机化系统和最小化随机算法将患者分为安慰剂组64例和便秘通组65例进行随机对照研究,之后有89例患者加入为期12周的延伸研究。有效性的主要研究终点是2周治疗期间出现自发排粪(SBM)反应者的比例,次要研究终点包括每周SBM频率、完全自发排便(CSBM)和不费力SBM。安全性评估包括治疗出现的不良反应(TEAEs)、阿片类戒断量表(COWS)评分及评估疼痛强度的11点数字评定量表(NRS)评分。比较安慰剂组与便秘通组的有效性和安全性,并分析延伸组的安全性。结果便秘通组、安慰剂组、延伸研究组患者的人口统计学信息和基线资料比较,差异无统计学意义(P>0.05)。便秘通组与安慰剂组出现SBM反应者的比例分别为72.3%(47/65)和34.4%(22/64),两组出现SBM反应者的比例比较,差异有统计学意义(χ^2=18.651,P<0.001)。便秘通组和安慰剂组基线SBMs比较,差异无统计学意义(P>0.05);便秘通组SBMs、CSBMs、不费力SBMs高于安慰剂组(P<0.05)。安慰剂组与便秘通组TEAEs和退出研究发生情况比较,差异无统计学意义(P>0.05);便秘通组腹泻发生率高于安慰剂组,差异有统计学意义(P<0.05)。延伸组TEAEs、退出研究、腹泻发生率分别为28.0%(25/89)、9.0%(8/89)、15.7%(14/89)。便秘通组和安慰剂组基线、第1次给药后1、8、15 d COWS评分比较,差异无统计学意义(P>0.05)。基线、给药前1 d、给药后1、8、29、57、85 d延伸组COWS评分分别为(1.51±0.57)(1.67±0.74)(1.58±0.56)(1.58±0.67)(1.58±0.58)(1.63±0.55)(1.60±0.52)分。便秘通组和安慰剂组基线、给药后1~14 d NRS评分比较,差异均无统计学意义(P>0.05)。结论便秘通治疗癌症患者OIC疗效确切,安全性好。

Background Opioid-induced constipation(OIC)is often seen in patients with moderate to severe cancer pain using opioids.OIC can cause many patients to be forced to reduce or discontinue the use of opioids,which makes the treatment of OIC critical in cancer patients.Objective An randomized controlled trial and an extended study were used to assess the efficacy and safety of"Bianmitong"on OIC in patients with cancer.Methods From January 2017 to February 2018,129 cancer patients with OIC in the Department of Oncology in Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University were enrolled in the study.Patients were divided into a placebo group of 64 patients and a Bianmitong group of 65 patients using a central randomization system and a minimized randomized algorithm for randomized controlled trials.After that,89 patients were enrolled in a 12-week extension study.The primary end point of efficacy was the proportion of spontaneous bowel movement(SBM)responders during the 2-week treatment period.The secondary study endpoints included weekly SBM frequency,complete spontaneous bowel movement(CSBM),and effortless SBM.Safety assessments included treatment-emergent adverse effects(TEAEs),Clinical Opiate Withdrawal Scale(COWS)scores,and an 11-point Numeric Rating Scale(NRS)scores for assessing pain intensity.The efficacy and safety of the placebo group and the Bianmitong group were compared and the safety of the extended group was analyzed.Results There were no significant differences in demographic information and baseline data between the Bianmitong group,the placebo group,and the extended group(P>0.05).The proportion of SBM responders in the Bianmitong group and placebo group were 72.3%(47/65)and 34.4%(22/64),respectively.The proportion of SBM responders in the two groups was statistically significant(χ^2=18.651,P<0.001).There was no significant difference in the baseline SBMs between the Bianmitong group and the placebo group(P>0.05).The SBMs,CSBMs,and effortless SBMs in the Bianmitong group were higher than those in the placebo group(P<0.05).There was no significant difference in TEAEs and the situation of withdrawal between the placebo group and the Bianmitong group(P>0.05).The incidence of diarrhea in the Bianmitong group was higher than that in the placebo group(P<0.05).The incidence of TEAEs,withdrawal,and diarrhea in the extended group were 28.0%(25/89),9.0%(8/89),and 15.7%(14/89).There was no significant difference in the COWS scores between the Bianmitong group and the placebo group at baseline and 1 d,8 d,and 15 d after the first dose(P>0.05).The COWS scores of the extended group at baseline,1 day before treatment,and 1 d,8 d,29 d,57 d,and 85 d after treatment were(1.51±0.57)(1.67±0.74)(1.58±0.56)(1.58±0.67)(1.58±0.58)(1.63±0.55)and(1.60±0.52),respectively.There were no significant differences in the NRS scores between the Bianmitong group and the placebo group at baseline and 1-14 d after treatment(P>0.05).Conclusion Bianmitong treatment of cancer patients with OIC is effective and safe.