Kessoku Takaomi, Akamatsu Toshikazu, Morioka Yasuhide, Yokota Takaaki, Kobayashi Masayuki, Uchida Kohei, Koretaka Yuichi, Nakajima Atsushi
Department of Palliative Medicine and Gastroenterology, International University of Health and Welfare Narita Hospital, Narita, Chiba, Japan.
Department of Gastroenterology, International University of Health and Welfare Graduate School of Medicine, Narita, Chiba, Japan.
Jpn J Clin Oncol. 2025 Jan 8;55(1):40-48. doi: 10.1093/jjco/hyae135.
To evaluate the additive effect of naldemedine tosylate (naldemedine) on opioid-induced constipation in cancer patients insufficiently responding to magnesium oxide treatment.
We combined two randomized, double-blind, placebo-controlled, phase IIb and III trials of naldemedine and conducted a post hoc subgroup analysis. We evaluated the effect and safety of naldemedine in 116 patients who received naldemedine in addition to magnesium oxide (naldemedine group) and 117 patients who received placebo in addition to magnesium oxide (placebo group). Both groups included patients insufficiently responding to magnesium oxide for opioid-induced constipation. Effect was assessed using spontaneous bowel movement responder rate, complete spontaneous bowel movement responder rate, changes in spontaneous bowel movements and complete spontaneous bowel movements. Safety was also assessed.
During the 2-week treatment period, the responder rates for spontaneous bowel movement and complete spontaneous bowel movement were 73.3 and 43.1% in naldemedine group, respectively, which were significantly higher (P < 0.0001) than 41.9 and 14.5% in placebo group, respectively. Median time to first spontaneous bowel movement and first complete spontaneous bowel movement was significantly shorter (P < 0.0001) in the naldemedine group (4.0 and 21.3 h, respectively) than in the placebo group (27.7 and 211.7 h, respectively). The incidence of adverse events and diarrhoea was significantly higher (P < 0.05) in the naldemedine group than in the placebo group, while the incidence of serious adverse events and severe diarrhoea was not significantly different between the naldemedine and placebo groups.
The study suggested the addition of naldemedine as an effective treatment option for opioid-induced constipation in cancer patients insufficiently responding to magnesium oxide treatment.
评估甲苯磺酸纳洛酮（纳洛酮）对氧化镁治疗反应不佳的癌症患者阿片类药物所致便秘的附加疗效。
我们合并了两项关于纳洛酮的随机、双盲、安慰剂对照的IIb期和III期试验，并进行了事后亚组分析。我们评估了116例除氧化镁外还接受纳洛酮治疗的患者（纳洛酮组）和117例除氧化镁外还接受安慰剂治疗的患者（安慰剂组）中纳洛酮的疗效和安全性。两组均纳入了对氧化镁治疗阿片类药物所致便秘反应不佳的患者。疗效通过自发排便反应率、完全自发排便反应率、自发排便和完全自发排便的变化来评估。同时也评估了安全性。
在为期2周的治疗期内，纳洛酮组自发排便和完全自发排便的反应率分别为73.3%和43.1%，显著高于安慰剂组的41.9%和14.5%（P<0.0001）。纳洛酮组首次自发排便和首次完全自发排便的中位时间（分别为4.0小时和21.3小时）显著短于安慰剂组（分别为27.7小时和211.7小时）（P<0.0001）。纳洛酮组不良事件和腹泻的发生率显著高于安慰剂组（P<0.05），而纳洛酮组和安慰剂组严重不良事件和严重腹泻的发生率无显著差异。
该研究表明，对于对氧化镁治疗反应不佳的癌症患者，添加纳洛酮是治疗阿片类药物所致便秘的有效选择。
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