Wallace, M., Rauck, R.L., Moulin, D., Thipphawong, J., Khanna, S., & Tudor, I.C. (2008). Conversion from standard opioid therapy to once-daily oral extended-release hydromorphone in patients with chronic cancer pain. Journal of International Medical Research, 36, 343–352.

To assess the efficacy and tolerability of oral once-daily extended-release hydromorphone in the treatment of chronic cancer pain

The study period consisted of three phases. In the first, study participants were stabilized on previous opioid therapy. This phase lasted for at least three consecutive days on which the total daily dose remained unchanged and fewer than four rescue doses were taken. Visit 1 occurred in this phase. The second phase consisted of conversion to once-daily extended-release hydromorphone. Dose conversion was 5:1 morphine to hydromorphone, with a minimum starting dose of 8 mg hydromorphone. In cases of conversion from transdermal fentanyl, initial hydromorphone was 8 mg for each 25 mg/hour fentanyl. Phase 3 consisted of hydromorphone titration over 3–21 days Visit 2 occurred during phase 3. Each patient's dose was titrated in increments of 25%–100% of current hydromorphone dose. If not stabilized after 21 days, patients were discontinued from the study. Participants who achieved stabilization for 14 days were in maintenance phase (visit 3) and were treated on an outpatient basis through five study visits. Visit 4 was at the midpoint of the maintenance phase. Visit 5 was at the end of the phase. Immediate-release hydromorphone was available for the treatment of breakthrough pain.

The number of enrollees was 148. Of the enrollees, 127 patients received the study medication and 67% completed the study. Patients received at least 45 mg morphine and had stable analgesic requirements.

• Multicenter
• 30 sites throughout the United States and Canada

Open-label, repeated-dose, single-treatment study

• Short Form of the Brief Pain Inventory (BPI)
• Adverse events
• Scale comprising rankings of worst, least, and average, to measure pain intensity
• Scale, 0–10, to measure pain
• Scale, 0%–100%, to measure pain relief
• Scale, 0–10, to measure the extent to which pain interfered with activity, mood, walking, work, relationships, sleep, and enjoyment of life
• Scale, comprising five points, to measure patients' and investigators' perceptions of medication's overall effectiveness

Dose stabilization occurred in 119 of 127 patients (94%); 77% of patients achieved stabilization without titration. Mean BPI pain intensity and pain interference scores decreased significantly. Mean pain relief level remained stable after conversion and throughout treatment. Adverse events were as expected. Authors noted no clinically significant changes in vital signs. Of all patients, 87% received hydromorphone for seven days or longer; 40%, for 25 days or longer. Of all patients, 94% achieved dose stabilization. Mean time to dose stabilization was 3.6 days. Dose increased 38% from initiation to stabilization but decreased slightly at the end of the maintenance phase. Frequency of rescue medication declined. Ratings indicated a decrease in pain, but the decrease of pain intensity on average was the only significant pain-related statistic (p < 0.001). Decreases in pain intensity were accompanied by a significant decrease in pain interference scores for all categories (p < 0.05). Of all patients, 83% experienced adverse events (nausea, constipation, vomiting, diarrhea, and somnolence). Serious adverse events occurred in 20 patients (16%). Authors reported that only one of these serious adverse events, confusion accompanied by hallucinations, was due to hydromorphone. Four deaths occurred during the study, all due to disease, not treatment.

Patients with chronic cancer pain can easily undergo conversion from previous opioid to stabilization on once-daily oral extended-release hydromorphone. Authors noted that use of this form of hydromorphone offered acceptable clinical efficacy and safety and the convenience of once-daily dosing. Authors concluded that the 5:1 ratio conversion was effective and that the conversion was not a problem for most patients. Adverse events were consistent with those expected with the use of other opiods.

• The study had a risk of bias due to the open-label design and lack of control group.
• Patients’ previous opioid use was not standardized.
• The pharmaceutical and medical systems company Alza sponsored the study. Some investigators had conflicts of interest due to affiliation with pharmaceutical companies.