ABSTRACT
OBJECTIVES: Opioid availability for the palliative care of patients with advanced cancer is increasing globally. However, opioid availability remains extremely low in Japan. We investigated whether pain is appropriately controlled by low-dose opioid prescriptions in patients with advanced cancer in Japan. METHODS: A web-based nationwide survey for caregivers from 2000 community comprehensive support care centers was performed in Japan to assess details about pain in the 30 days before patients died of end-stage cancer. Separately, the data for opioid prescription doses and medical services in the 90 days before the death of patients with cancer were extracted from a health insurance claim database. RESULTS: Responses from 1034 responders were retrieved and 665 patients were included. In total, 254 patients (38.2%) complained of severe-to-intolerable cancer-related pain. The median cumulative prescription dose of opioids in the 90 days before patient death was 311.0 mg by oral morphine equivalent doses. Multiple regression analyses across prefectures revealed that the proportion of patients with severe-to-intolerable cancer-related pain was negatively associated with the cumulative opioid consumption expressed as morphine-equivalent doses within 90 days before death. CONCLUSIONS: The very low availability of opioids for patients with end-stage cancer could result in high rate of severe-to-intolerable cancer-related pain patients. There were several limitations in this study, and the interpretations of the findings should be carefully. However, the increase in the absolute dose of opioids could improve the palliative care framework to the pain control levels of the global standard.
ABSTRACT
Purpose This randomized, double-blind, multicenter study aimed to determine the dose of naldemedine, a peripherally-acting µ-opioid receptor antagonist, for future trials by comparing the efficacy and safety of three doses of naldemedine versus placebo in patients with cancer and opioid-induced constipation. Methods Patients ≥ 18 years old with cancer, an Eastern Cooperative Oncology Group performance status ≤ 2, who had been receiving a stable regimen of opioid analgesics for ≥ 2 weeks, had at least one constipation symptom despite laxative use, and no more than five spontaneous bowel movements (SBMs) during the past 14 days, were randomly assigned (1:1:1:1) to oral, once-daily naldemedine 0.1, 0.2, or 0.4 mg, or placebo, for 14 days. The primary end point was change in SBM frequency per week from baseline during the treatment period. Secondary end points included SBM responder rates, change from baseline in the frequency of SBM without straining, and complete SBM. Safety was also assessed. Results Of 227 patients who were randomly assigned, 225 were assessed for efficacy (naldemedine 0.1 mg, n = 55; 0.2 mg, n = 58; 0.4 mg, n = 56; placebo, n = 56) and 226 for safety. Change in SBM frequency (primary end point) was higher with all naldemedine doses versus placebo ( P < .05 for all comparisons), as were SBM responder rates and change in complete SBM frequency. Change in SBM frequency without straining was significantly improved with naldemedine 0.2 and 0.4 (but not 0.1) mg versus placebo (at least P < .05). Treatment-emergent adverse events were more common with naldemedine (0.1 mg: 66.1%; 0.2 mg: 67.2%; 0.4 mg: 78.6%) than placebo (51.8%); the most common treatment-emergent adverse event was diarrhea. Conclusion Fourteen-day treatment with naldemedine significantly improved opioid-induced constipation in patients with cancer and was generally well tolerated. Naldemedine 0.2 mg was selected for phase III studies.
