• David C Currow, Christine McDonald, Sheila Oaten, Bernadette Kenny, Peter Allcroft, Peter Frith, Michael Briffa, Miriam J Johnson, and Amy P Abernethy.
• Discipline, Palliative and Supportive Services, Flinders University, Bedford Park, SA, Australia. david.currow@flinders.edu.au
• J Pain Symptom Manage. 2011 Sep 1;42(3):388-99.

ContextRandomized controlled trials can answer questions of efficacy, but long-term pharmacovigilance studies generate complementary safety data.ObjectivesLevel I evidence supports short-term efficacy of opioids in reducing chronic refractory dyspnea. This study aimed to determine the minimum effective once-daily dose of sustained-release morphine, and whether net clinical benefits are sustained safely.MethodsIn a Phase II dose increment study, 10mg daily of sustained-release morphine was administered, and increased in nonresponders by 10mg daily each week to a maximum of 30 mg daily. The participant was withdrawn if there were unacceptable side effects or no response to maximum dose. If participants had a 10% improvement in dyspnea over their own baseline, they joined a long-term Phase IV effectiveness/safety study at that dose. Complying with Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines, response and side effects are described, with demographic and clinical characteristics of responders.ResultsEighty-three participants (53 males, mean age 75 years, 54% with chronic obstructive pulmonary disease) provided more than 30 patient-years of data. Fifty-two participants derived ≥ 10% benefit (on average 35% improvement over baseline), giving a response rate of 62% (number needed to treat of 1.6: number needed to harm 4.6); for 70%, this dose was 10mg/24h. Benefit was maintained at three months for 28 (33%) people. Ranking of breathlessness was reduced significantly (P<0.001), but constipation increased (P<0.001) despite laxatives. There were no episodes of respiratory depression or hospitalizations as a result of the sustained-release morphine. Overall, one in three people continued to derive benefit at three months.ConclusionTen milligrams of sustained-release oral morphine once daily is safe and effective for most people who respond.Copyright © 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

17 keywords...

hide…