Lee, K.H., Kim, M.K., Hyun, M.S., Kim, J.Y., Park, K.U., Song, H.S., . . . Cho, Y.Y. (2012). Clinical effectiveness and safety of OROS® hydromorphone in break-through cancer pain treatment: A multicenter, prospective, open-label study in Korean patients. Journal of Opioid Management, 8, 243–252.

To evaluate the effectiveness of OROS hydromorphone in reducing the use of medication for breakthrough pain (BTP) in Korean patients with chronic cancer pain

Patients were stabilized on the existing pain regimen for three days. After stabilization, pain medication was converted to OROS hydromorphone at a dose equivalent to oxycodone in effectiveness. Dose equivalence was calculated using the ratio 2.5:1 controlled-release oxycodone to hydromorphone hydrochloride. The minimum starting dose of hydromorphone was 8 mg, which was provided in the form of 8, 16, or 32 mg tablets. Patients took the medication at 8 am each morning, swallowing tablets whole, with water, and without chewing, dividing, or crushing. Immediate-release hydromorphone was used as the rescue medication at a dose equaling 10%–15% of OROS hydromorphone. No other opioid medications were permitted postconversion to OROS hydromorphone. Patients were allowed to use nonopioid and adjuvant analgesics. On day 7, if the patient required more than four rescue doses per day, medication was increased in increments of 8 or 16 mg. Investigators collected data at baseline and on days 7 and 14.

• The sample was composed of 114 patients.
• Mean patient age was 58.2 years (SD = 11 years).
• Of all patients, 67% were male and 33% were female.
• The sample comprised multiple cancer sites. Of all cancer diagnoses, 84% had metastasized.

• Multisite
• Outpatient
• South Korea

• Phases of care: multiple phases of care
• Clinical application: palliative care

Prospective open-label phase IV study

• Pain diary, to record frequency of BTP and its subtypes
• Mean of medication frequency of BTP (Investigators calculated the mean by averaging the use of BTP medications for the three days prior to the study visit.)
• Korean Brief Pain Inventory, 0–10 scale, to measure pain intensity
• Scale, 0–100, to measure pain relief
• Scale, 0–10, to measure pain-related interference with general activities, mood, ability to walk, normal work activities, relationships with others, sleep, and enjoyment of life
• European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire

Compared to the mean of BTP frequencies at baseline, the mean of BTP frequencies decreased significantly (p < 0.001) on days 7 and 14. Also compared to baseline, BTP subtypes decreased on days 7 and 14. Compared to baseline measures, measures of pain intensity at its worst (p < 0.001) and average pain intensity (p < 0.005) decreased on day 14. Compared to baseline measures, measures of physical functioning improved significantly (p = 0.015) on day 14. Emotional, cognitive, and social functioning were stable after drug conversion (p > 0.05). At the end of the trial, 61.2% of patients rated the medication as effective and 91.2% of patients reported mild or moderate adverse events. (Authors reported that 32% of adverse events were considered related to study treatment.) Of all patients, 88% preferred the study regimen to their previous regimen, based on ease of use.

OROS hydromorphone was effective in reducing pain intensity in patients with chronic cancer pain. Physical function improved over 14 days while cognitive and emotional functioning remained intact. Although most patients reported adverse events, the majority of events were mild or moderate and unrelated to the study drug. In regard to ease of use, the overwhelming majority of patients preferred the study regimen to their previous regimen.

The study had risks of bias due to no control group, no blinding, and no random assignment.

Because this study showed that OROS hydromorphone therapy could decrease pain severity and that patients found the medication easy to use, clinicians should consider the drug in the treatment of patients with chronic cancer-related pain. The results of this study warrant a randomized, blinded trial.