Comparison of the Tolerability Profile of Controlled-Release Oral Morphine and Oxycodone for Cancer Pain Treatment. An Open-Label Randomized Controlled Trial.

CONTEXT: Oxycodone and morphine are recommended as first-choice opioids for moderate/severe cancer pain, but evidence about their relative tolerability has significant methodological limitations.

OBJECTIVES: This study was mainly aimed at comparing the risk of developing adverse events (AEs) with controlled-release oral morphine vs. oxycodone; secondary aims were comparing their analgesic efficacy and testing heterogeneity in tolerability across different age and renal function subgroups.

METHODS: An open-label multicenter RCT (EudraCT number: 2006-003151-21) was carried out in patients with moderate/severe cancer pain. At baseline, 7 and 14 days, patients scored on 0-10 rating scales (0-10 numerical rating scale) the intensity of pain and of a list of common opioid side effects. The primary end point was the percentage of patients reporting an AE (a worsening ≥ 2 points on any of the listed side effects); tolerability by subgroups and average follow-up pain intensity were compared through regression models.

RESULTS: One hundred eighty-seven patients were enrolled (47% of originally planned). Intention to treat (ITT) analysis (N = 185, morphine 94, oxycodone 91) did not show any difference in the risk of developing AEs (risk difference -0.6%, 95% CI -11.0% to 9.9%) nor in analgesia (0-10 numerical rating scale pain intensity difference -0.28, 95% CI -0.83 to 0.27). No evidence of heterogeneity of tolerability across age and renal function patient subgroups emerged.

CONCLUSION: This trial failed to show any difference in tolerability and analgesic efficacy of morphine and oxycodone as first-line treatment for moderate/severe cancer pain but results interpretation is difficult due to lack of power, potential bias from open-label design, and concerns about assay sensitivity. These data, however, can significantly contribute to future meta-analyses comparing WHO Step-III opioids and are relevant in designing future randomized studies.