Gonzalez-Barboteo, J., Alentorn, X.G., Manuel, F.A., Candel, V.A., Eito, M.A., Sanchez-Magro, I., . . . Porta-Sales, J. (2014). Effectiveness of opioid rotation in the control of cancer pain: The ROTODOL study. Journal of Opioid Management, 10, 395–403. 

To assess the effectiveness of and adverse events associated with opioid rotation for the management of cancer-related pain

All consecutive patients who attended the clinics of participating hospitals were eligible. A single opioid conversion table was used by all participants. If a rotation was used because of pain and toxicity, the baseline dosage was reduced by 25%–50% prior to the change. If no toxicity was present, an equivalent dose was used. Pain was assessed days prior to the implementation of the rotation and one week postimplementation. During the week, changes in opioid dosage were allowed and recorded. Patients were followed for 90 days.

• N = 67  
• MEDIAN AGE = 61 years (range 27–91 years)
• MALES: 73.1%, FEMALES: 26.9%
• KEY DISEASE CHARACTERISTICS: Various tumor sites; lung cancer was most prevalent; most had advanced disease
• OTHER KEY SAMPLE CHARACTERISTICS: Pain was nociceptive in 53.6% and mixed or neuropathic in 46.3%

• SITE: Multi-site  
• SETTING TYPE: Outpatient  
• LOCATION: Spain

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care 

Observational

• Numeric Rating Scale (NRS) for average and breakthrough pain
• Number of breakthrough episodes per day
• Common Terminology Criteria for Adverse Events (CTCAE)

About 89.5% of patients had one opioid rotation. The most common drugs used for the rotation were morphine, fentanyl, and transdermal buprenorphine. The most common switch was from fentanyl to morphine. The rotation was effective in 75.4% of patients for reducing average pain and in 57.8% for breakthrough pain. Average pain decreased at day 7 (p < 0.001) by four points, breakthrough intensity decreased by four points (p < 0.001), and the number of breakthrough episodes decreased on average from three to one (p < 0.001). Among patients in whom the rotation was effective, there were no significant differences between pre- and postequivalent doses of opioids. In 10 switches (out of a total of 75), there were no toxicities postrotation at one week. Rotations to methadone appeared to be associated with more postrotation adverse events.

The results of this study suggest that opioid rotation can be effective for pain management and the reduction of opioid-associated toxicities in most patients. Rotations to methadone appeared to be associated with more toxicities than rotations to other medications.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Questionable protocol fidelity
• Other limitations/explanation: Throughout the study period, the total opioid doses were not maintained although there was no overall significant difference in the morphine equivalents found. The study reported results at only one week. There was no information on the length of time patients received opioids prior to the study or the severity of toxicities prior to the rotation. There was no information regarding any potential adjuvant medication use.

In patients with severe cancer-related pain, opioid rotations may be beneficial for improving pain management and addressing opioid-related toxicities. However, the duration of this effect is not clear. These results suggest that switching to methadone might not be the best choice for reducing toxicities.