Effect of Opioid Exposure on Efficacy and Tolerability of Sublingual Fentanyl and Subcutaneous Morphine for Severe Cancer Pain Episodes. Secondary Analysis From a Double-Blind Double-Dummy, Randomized Trial

Context: Few studies have addressed the impact of previous opioid exposure on the effect of opioids for the treatment of severe cancer pain episodes. Objectives: We aimed to test whether previous exposure to higher opioid doses was associated with a reduced analgesic effect of fentanyl sublingual tablets (FST) and subcutaneous morphine (SCM) and whether it had an influence on their relative effect. Methods: This is a secondary analysis of a placebo-controlled randomized trial comparing 100 μg FST with 5 mg SCM for the acute treatment of severe cancer pain episodes. The effect of previous opioid exposure (oral morphine equivalent daily dose from 20 to 120 mg) on pain intensity difference (PID) and side effects at 30 and 60 minutes after administration (PID 0-30 minutes, PID 0-60 minutes, and adverse events 30-60 minutes) and on re-medication for inefficacy, was studied by multivariable linear and logistic regression models and statistical tests for interaction. Results: A total of 114 patients were enrolled. Results indicate modest and nonstatistically significant effect of previous opioid exposure on all the outcomes examined (P = 0.11, P = 0.35, P = 0.07, and P = 0.52, respectively, for PID 0-30 minutes, re-medication, PID 0-60 minutes, and adverse events 30-60 minutes). Nonstatistically significant tests for interaction for all models indicated a lack of impact of previous opioid exposure on the difference in the analgesic effect between treatments. Conclusion: In this study, we could not demonstrate an effect of previous opioid exposure, from 20 to 120 mg oral morphine equivalent daily dose, on the absolute and relative efficacy and tolerability of 100 μg FST and 5 mg SCM for severe cancer pain episodes.