Efficacy and safety of naldemedine for opioid-induced constipation in older patients with cancer: a retrospective study.

BACKGROUND: Opioids are pain relievers that are often associated with opioid-induced constipation (OIC) that worsens with age. We performed a multicenter, retrospective analysis on the efficacy and safety of naldemedine, an opioid receptor antagonist, in treating OIC in patients with cancer (age >75 years). METHODS: The electronic medical records of cancer patients who received naldemedine at 10 Japanese institutions between 7 June 2017 and August 31, 2019, were retrieved. Patients aged ≥75 years who were treated with naldemedine for the first time and hospitalized for at least 7 days before and after initiating naldemedine therapy were included in this analysis. RESULTS: Sixty patients were observed for at least 7 days before and after starting naldemedine. The response rate was 68.3%, and the frequency of bowel movements increased significantly after naldemedine administration in the overall population ( P  < 0.0001) and among those who defecated <3 times/week before naldemedine administration ( P  < 0.0001). Diarrhea was the most frequent adverse event in all grades, observed in 45% of patients, of which 92.6% were Grade 1 or 2. Grade 4 or higher adverse events, including death, were not observed. CONCLUSION: Naldemedine exhibits significant efficacy and safety in OIC treatment in older patients with cancer.

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

BACKGROUND: Gastrointestinal cancers are one of the most common cancer cases worldwide. Cancer treatment is multidisciplinary, which includes opioid pain management. Opioid analgesics cause opioid-induced 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. Twenty-one 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% confidence interval (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. CONCLUSIONS: The results of the study suggest that naldemedine is effective and safe in clinical practice for gastrointestinal cancer treatment.

Efficacy and Safety of Naldemedine Administration for Opioid-Induced Constipation in Cancer Patients with Poor Performance Status.

Background: Constipation is a concern among patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 3 and 4. Objectives: To assess naldemedine's efficacy and safety in cancer patients on opioids with poor PS. Design: Multicenter, retrospective study. Setting/Subjects: Japanese cancer patients with ECOG performance status 3 or 4 who received naldemedine. Measurements: Frequency of defecations before/after naldemedine use. Responders were patients whose defecation frequency increased to ≥3 times/week, from baseline ≥1 defecations/week over seven days after naldemedine administration. Results: Seventy-one patients were analyzed; 66.1% were responders (95% confidence interval: 54.5%-76.1%). Defecation frequency increased significantly after naldemedine in the overall population (6 vs. 2, p < 0.0001) and among those who defecated <3 times/week before naldemedine (4.5 vs. 1, p < 0.0001). Diarrhea (38.0%) of all grades was the most common adverse event; 23 (85.2%) events were classified as Grade 1 or 2. Conclusion: Naldemedine is effective and safe among cancer patients with poor PS.

A Retrospective Study of the Efficacy and Safety of Naldemedine for Treatment of Opioid-Induced Constipation in Patients with Hepatobiliary Pancreatic Cancer.

Background and Objectives: Opioid analgesics, which are used for cancer-related pain management, cause opioid-induced constipation (OIC). 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 hepatobiliary pancreatic cancers. We performed a multi-institutional study on the efficacy and safety of naldemedine in patients with hepatobiliary pancreatic cancer using opioids in clinical practice. Materials and Methods: We retrospectively evaluated patients with hepatobiliary pancreatic cancer (including liver, biliary tract, and pancreatic cancers) treated with opioids and naldemedine during hospitalization at ten institutions in Japan from June 2017 to August 2019. We assessed the frequency of bowel movements before and after the initiation of naldemedine therapy. Responders were defined as patients who defecated ≥3 times/week, with an increase from a baseline of ≥1 defecations/week over seven days after the initiation of naldemedine administration. Results: Thirty-four patients were observed for one week before and one week after starting naldemedine. The frequency of bowel movements increased by one over the baseline frequency or to at least thrice per week in 21 patients. The response rate was 61.7% (95% confidence interval: 45.4-78.0%). The median number of weekly bowel movements before and after naldemedine treatment was 2 (range: 0-9) and 6 (range: 1-17), respectively, in the overall population (n = 34); the increase in the number of bowel movements following naldemedine administration was statistically significant (Wilcoxon signed-rank test, p < 0.0001). Diarrhea was the predominant gastrointestinal symptom, and 10 (29.4%) patients experienced grade 1, grade 2, or grade 3 adverse events. The only other adverse event included fatigue in one patient; grade 2-4 adverse events were absent. Conclusions: Naldemedine is effective, and its use may be safe in clinical practice for patients with hepatobiliary pancreatic cancer receiving opioid analgesics.

A retrospective study of the efficacy and safety of naldemedine for opioid-induced constipation in thoracic cancer patients.

BACKGROUND: We conducted a multicenter, retrospective study on the efficacy and safety of naldemedine in thoracic cancer patients using opioids in clinical practice. METHODS: We retrospectively evaluated thoracic cancer patients treated with naldemedine at 10 institutions in Japan. Clinical data of patients administered naldemedine between June 2017 and August 2019 were extracted from electronic medical records. Inclusion criteria were as follows: (i) patients hospitalized for at least seven days before and after naldemedine administration, and (ii) those whose frequency of defecation was entered in the medical records. RESULTS: Forty patients were analyzed, and defecation frequency was observed for at least seven days before and after naldemedine administration. The response rate was 65.0% (95% CI: 50.2%-79.7%). The number of defecations increased significantly after naldemedine administration in the overall population, as well as among only those who defecated <3 times/week before naldemedine administration, and those that were administered ≥30 mg/day of morphine equivalent. Diarrhea was the most common adverse event in all grades, occurring in 11 patients (27.5%), of which 9 (81.8%) were grade 1 or 2. None of the patients experienced grade 4 or higher adverse events. CONCLUSION: The efficacy and safety of naldemedine for thoracic cancer patients in clinical practice were comparable with those of prospective studies, which suggest that naldemedine may be effective and feasible for most thoracic cancer patients.

Efficacy and Safety of Naldemedine for Patients with Cancer with Opioid-Induced Constipation in Clinical Practice: A Real-World Retrospective Study.

The efficacy and safety of naldemedine for opioid-induced constipation in patients with cancer has not been investigated in clinical practice. We conducted a multicenter, retrospective study to assess the effects of naldemedine among 10 Japanese institutions between June 2017 and August 2019. We evaluated the number of defecations 7 days before and after naldemedine administration. A total of 149 patients (89 male) with a median age of 72 years (range, 38−96) were included. The performance status was 0−1, 2, and ≥3 in 40, 38, and 71 patients, respectively. The median opioid dose in oral morphine equivalents was 30 mg/day (range: 7.5−800 mg). We observed 98 responders and 51 non-responders. The median number of defecations increased significantly in the 7 days following naldemedine administration from three to six (p < 0.0001). Multivariate analysis revealed that an opioid dose <30 mg/day [odds ratio, 2.08; 95% confidence interval, 1.01−4.32; p = 0.042] was significantly correlated with the effect of naldemedine. Diarrhea was the most common adverse event (38.2%) among all grades. The efficacy and safety of naldemedine in clinical practice are comparable to those of prospective studies, suggesting that it is effective in most patients.

Real-World Patient Characteristics and Treatment Patterns of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients with Cancer: A Multicenter Retrospective Chart Review Study.

Background and Objectives: Naldemedine is a peripherally acting µ-opioid receptor antagonist that improves opioid-induced constipation. Although clinical trials have excluded patients with poor performance status (PS) and those started on naldemedine early after opioid initiation, clinical practice has used naldemedine for the same patients. Therefore, we investigated the treatment patterns of naldemedine in a real-world setting. Materials and Methods: This was a multicenter, retrospective chart review study of opioid-treated patients with cancer receiving naldemedine. Adverse events that occurred within 7 days of naldemedine initiation were evaluated in those who received one or more doses of the same. Effectiveness was assessed in patients who used naldemedine for more than 7 days. Results: A total of 296 patients satisfied the eligibility criteria, among whom 129 (43.6%) had a PS of ≥3 and 176 (59.5%) started naldemedine within 2 weeks of opioid initiation. Moreover, 203 (79.6%) patients had ≥3 bowel movements per week. Incidences of all grades of diarrhea and abdominal pain were 87 (29.4%) and 12 (4.1%), respectively. No patient had grade 4 or higher adverse events. Conclusions: Although nearly half of the patients receiving naldemedine in clinical practice belonged to populations that were not included in the clinical trials, our results suggested that naldemedine in clinical practice had the same efficacy and safety as that in clinical trials.