Efficacy and safety of naldemedine treatment for opioid-induced constipation in gastrointestinal cancer: a retrospective analysis

Abstract

Background: Gastrointestinal cancers are one of the most common cancer cases worldwide. Cancer treatment is multidisciplinary, which includes opioid pain management. Opioid analgesics cause opioidinduced constipation (OIC) with the onset of effect. Naldemedine, a peripheral opioid receptor antagonist, is an OIC-modifying agent, but no focused efficacy and safety analysis has been conducted for its use in gastrointestinal cancers.Methods: We retrospectively evaluated patients with gastrointestinal cancer treated with naldemedine at ten institutions in Japan from June 2017 to August 2019. Patients with gastrointestinal cancer who initiated treatment with opioids during hospitalization and were treated with naldemedine for the first time were included in the study. The gastrointestinal cancer types included were esophageal, gastric, small bowel, and colorectal cancers. We assessed the defecation frequency before and after the initiation of naldemedine use.Responders were defined as patients who defecated three or more times/week, with an increase from the baseline of one or more bowel movements/week over seven days after starting naldemedine.Results: Thirty-three patients were observed for one week before and after starting naldemedine. Twentyone patients had an increase in defecation frequency of at least three times per week or at least once per week above the baseline. The response rate was 63.6% (95% CI: 46.6-77.9%). The median number of bowel movements for a week before and after the initiation of naldemedine treatment was 3 (range, 0-13) and 7 (range, 1-39), respectively, in the overall population (n=33), with a significant increase in defecation frequency following naldemedine administration (Wilcoxon signed rank test, P<0.005). Diarrhea was the predominant gastrointestinal symptom, with 13 (39.4%) patients experiencing grade 1 and none experiencing grade 3 or grade 4 adverse events. The frequency of other grade 1 adverse events was low abdominal pain in two patients, nausea in two patients, and anorexia in one patient, without any grade 2-4 adverse events.

A Systematic Review of Naldemedine and Naloxegol for the Treatment of Opioid-Induced Constipation in Cancer Patients

“…Diarrhea was the most common adverse event and occurred in 27.5% (11 patients) but was mild for most of them (9 patients). Another Japanese multi-center retrospective study examined 33 hospitalized patients with gastrointestinal cancers (esophageal, gastric, small bowel, and colorectal cancers) of which, again, 63.6% were considered responders, i.e., they had a significant increase in bowel movement frequency of at least three times per week or at least once per week above the baseline after initiation of naldemedine [ 36 ]. Mild diarrhea was again the most common adverse event and occurred in 39.45% (13 patients).…”