Morphine-methadone opioid rotation in cancer patients: analysis of dose ratio predicting factors

The dose ratio that is effective when switching opioid therapy from morphine to methadone in cancer patients varies widely. There are no conclusive data explaining the source of this variability. We analyzed 54 cancer patients undergoing opioid rotation to clarify those factors that influenced the morphine/methadone dose ratio (MMEDR) at Day 10 after the switch. Reasons for switching were uncontrolled pain (10 patients) or side effects (with or without pain, 44 patients). Initial MMEDR was 5:1 or 10:1 (82% or 18% of patients, respectively). Multivariate regression analysis was used to identify the demographic, cancer-related, and treatment-related variables that were potential predictors of MMEDR. Median previous morphine dose for the entire sample was 220 mg/day (range: 30-1000 mg/day). The stable MMEDR median was 5:1 (range: 2:1-15:1). In the univariate analysis, reasons for opioid rotation, age, and previous morphine doses were associated with MMEDR. Multiple linear regression analysis showed that only the reason for switching (pain vs. side effects; P<0.001) and previous morphine doses (lower vs. upper to 300 mg/day; P<0.001) were associated with MMEDR. From this analysis, the MMEDRs for patients rotated for side effects at 300 mg/day or more or less than 300 mg/day of morphine were 9.1:1 or 5.6:1, respectively, and the MMEDRs for those switched for pain at 300 mg/day or more or less than 300 mg/day of morphine were 4.9:1 or 3:1, respectively. Both the reasons for opioid rotation and previous morphine doses are predictive factors and should be used to select the MMEDR more accurately.