Nadstawek, J., Leyendecker, P., Hopp, M., Ruckes, C., Wirz, S., Fleischer, W., & Reimer, K. (2008). Patient assessment of a novel therapeutic approach for the treatment of severe, chronic pain. International Journal of Clinical Practice, 62, 1159–1167. 

• To assess the analgesic efficacy of prolonged-release (PR) oxycodone in combination with orally administered naloxone PR in patients with severe, chronic pain; to evaluate the efficacy of that combination in improving bowel function
• To evaluate the optimal dose ratio of oxycodone PR to naloxone PR
• To evaluate patients’ and investigators’ treatment preference

In this three-phase study, patients with inadequate pain control entered the titration period, with stabilization at 40, 60, or 80 mg oxycodone PR/day. Those on stable oxycodone dosing who used laxatives to have three bowel movements per week were entered in the maintenance phase after a seven-day run-in period. After patients were stabilized, they were randomized into three naloxone treatment groups or a placebo group. Oxycodone was given open label; naloxone was given in double-blind fashion. After a patient was in the maintenance phase, no titration of oxycodone PR doses was allowed. Those using laxatives were advised to stop unless no bowel movement had occurred for three days. Patients were studied for four weeks, then assessed in a two-week follow-up phase. In the follow-up phase, no one received naloxone PR.

• The intent-to-treat (ITT) group, defined as those who were randomized and received at least one dose of naloxone or placebo and had at least one efficacy assessment, comprised 196 patients; 166 patients completed the study.
• Patients were older than 18 years.
• The sample was 62.9% female and 37.1% male.
• Specific cancer type was not reported.

• Multisite
• Outpatient
• Twenty-eight centers in Germany, May 2002 to April 2003

Prospective randomized double-blind, parallel-group, phase II trial

• Rating scale (1 = very good, 7 = very poor), to measure efficacy and tolerability, used independently by investigators and patients
• Preference, in regard to tolerability and efficacy, for maintenance phase or titration–run-in phase (1 = titration–run-in, 2 = maintenance, 3 = no preference)

• The efficacy of the 2:1 dose ratio of oxycodone PR to naloxone PR was ranked as good or very good by 70.4% of patients and investigators.
• The tolerability of the 2:1 dose ratio was ranked as good or very good by 81.5% of patients and investigators.
• The majority of patients in the treatment arm preferred the maintenance phase, in which they received both medications.
• Naloxone PR had no impact on the analgesic efficacy of oxycodone PR; naloxone PR improved bowel function and reduced laxative intake.

Concurrent administration of oxycodone PR and naloxone PR is effective for the treatment of patients with severe chronic pain, cancer-related or not. Patients tolerated naloxone PR well; naloxone created no  additional untoward effects.

• Exclusion of patients with severe cardiovascular or pulmonary issues limits the applicability of findings to patients with advanced cancers and those taking more than five medications per week to control breakthrough pain.
• Oxycodone PR dosing was limited to 40–80 mg/day.

This study's results relate to pain control and bowel function of patients with cancer. Additional research, to investigate widening application of the findings, is warranted.