PDF(Pubmed)
Abstract：
BACKGROUND: Opioid-induced constipation (OIC) is a pervasive and distressing side effect of chronic opioid therapy in patients with cancer pain, significantly impacting their quality of life. Peripherally acting μ-opioid receptor antagonists (PAMORAS) were developed for treatment-resistant OIC but most studies were conducted with non-cancer patients.
OBJECTIVE: to discuss two oral formulations of PAMORAs, naldemedine and naloxegol, and to review available evidence of the effectiveness of these drugs for OIC in cancer patients.
METHODS: a comprehensive search to identify primary literature for either naldemedine or naloxegol for OIC in cancer patients.
RESULTS: Only three prospective randomized, double-blind, placebo-controlled clinical trials for naldemedine enrolling cancer patients were identified; the results of a subgroup analysis of two of those studies and two non-interventional post marketing surveillance studies of these trials are also reported here. For naloxegol, only two randomized controlled trials were identified; both were unsuccessful in enrolling sufficient patients. An additional four prospective non-interventional observational studies with naloxegol were found that enrolled cancer patients. There were significantly higher rates of responders in the PAMORA groups than in the placebo groups. The most common side effect for both PAMORAs was diarrhea.
CONCLUSIONS: All studies were industry-funded, and given that only three trials were randomized controlled studies, the overall quality of the studies was lacking.
CONCLUSIONS: Naldemedine or naloxegol appeared safe and useful in the treatment of OIC in cancer patients and may improve their quality of life. Larger-scale randomized placebo-controlled studies of PAMORAs in cancer patients would strengthen existing evidence.
OBJECTIVE: to discuss two oral formulations of PAMORAs, naldemedine and naloxegol, and to review available evidence of the effectiveness of these drugs for OIC in cancer patients.
METHODS: a comprehensive search to identify primary literature for either naldemedine or naloxegol for OIC in cancer patients.
RESULTS: Only three prospective randomized, double-blind, placebo-controlled clinical trials for naldemedine enrolling cancer patients were identified; the results of a subgroup analysis of two of those studies and two non-interventional post marketing surveillance studies of these trials are also reported here. For naloxegol, only two randomized controlled trials were identified; both were unsuccessful in enrolling sufficient patients. An additional four prospective non-interventional observational studies with naloxegol were found that enrolled cancer patients. There were significantly higher rates of responders in the PAMORA groups than in the placebo groups. The most common side effect for both PAMORAs was diarrhea.
CONCLUSIONS: All studies were industry-funded, and given that only three trials were randomized controlled studies, the overall quality of the studies was lacking.
CONCLUSIONS: Naldemedine or naloxegol appeared safe and useful in the treatment of OIC in cancer patients and may improve their quality of life. Larger-scale randomized placebo-controlled studies of PAMORAs in cancer patients would strengthen existing evidence.
摘要：
背景：阿片类药物诱导的便秘（OIC）是慢性阿片类药物治疗癌痛患者的一种普遍且令人痛苦的副作用，显著影响他们的生活质量。外周作用的μ-阿片受体拮抗剂（PAMORAS）被开发用于治疗抗性的OIC，但大多数研究是针对非癌症患者进行的。
目的：讨论PAMORAs的两种口服制剂，纳地梅定和纳洛昔果,并回顾这些药物对癌症患者OIC有效性的现有证据。
方法：是一项综合检索，旨在确定纳地米定或纳洛昔醇治疗癌症患者OIC的主要文献。
结果：只有三个前瞻性随机分组，双盲,我们确定了纳地米定癌症患者的安慰剂对照临床试验;本文还报道了其中两项研究的亚组分析结果和这些试验的两项非干预性上市后监测研究的结果.对于纳洛谢戈尔来说,仅确定了两项随机对照试验;两项试验均未成功纳入足够的患者.发现另外四项前瞻性非干预性观察性研究与纳洛谢戈尔一起招募了癌症患者。PAMORA组的应答者比率显著高于安慰剂组。两种PAMORA最常见的副作用是腹泻。
结论：所有研究均由行业资助，考虑到只有三项试验是随机对照研究，研究的整体质量缺乏.
结论：Naldemedine或Naloxegol在治疗癌症患者OIC中似乎是安全有效的，并且可以改善他们的生活质量。在癌症患者中进行大规模的PAMORAs随机安慰剂对照研究将加强现有的证据。
目的：讨论PAMORAs的两种口服制剂，纳地梅定和纳洛昔果,并回顾这些药物对癌症患者OIC有效性的现有证据。
方法：是一项综合检索，旨在确定纳地米定或纳洛昔醇治疗癌症患者OIC的主要文献。
结果：只有三个前瞻性随机分组，双盲,我们确定了纳地米定癌症患者的安慰剂对照临床试验;本文还报道了其中两项研究的亚组分析结果和这些试验的两项非干预性上市后监测研究的结果.对于纳洛谢戈尔来说,仅确定了两项随机对照试验;两项试验均未成功纳入足够的患者.发现另外四项前瞻性非干预性观察性研究与纳洛谢戈尔一起招募了癌症患者。PAMORA组的应答者比率显著高于安慰剂组。两种PAMORA最常见的副作用是腹泻。
结论：所有研究均由行业资助，考虑到只有三项试验是随机对照研究，研究的整体质量缺乏.
结论：Naldemedine或Naloxegol在治疗癌症患者OIC中似乎是安全有效的，并且可以改善他们的生活质量。在癌症患者中进行大规模的PAMORAs随机安慰剂对照研究将加强现有的证据。
