Open Access Open Access  Restricted Access Subscription or Fee Access

Clinical effectiveness and safety of OROS® hydromorphone in breakthrough cancer pain treatment: A multicenter, prospective, open-label study in Korean patients

Kyung Hee Lee, MD, Min Kyoung Kim, MD, Myung Soo Hyun, MD, Jin Young Kim, MD, Keon Uk Park, MD, Hong Suk Song, MD, PhD, Sun Ah Lee, MD, Won Sik Lee, MD, Sung Hwa Bae, MD, Hun Mo Ryoo, MD, Yoon Young Cho, MD


Objective: To evaluate the effectiveness of OROS® hydromorphone in reducing breakthrough pain (BTP) medication frequency in Korean patients with chronic cancer pain.

Settings and Design: Multicenter, prospective, open-label, phase IV study.

Participants: Patients with chronic malignant pain using immediate-release oxycodone more than two times per day for BTP.

Interventions: Patients were stabilized on their ongoing drug for 3 days immediately before baseline measurements (day 0). Medication was changed to OROS® hydromorphone at a dose equianalgesic to oxycodone using a 2.5:1 controlledrelease oxycodone to hydromorphone hydrochloride conversion ratio; the patients were observed for 7 days. Dose was titrated, if required, and the patients were observed for another 7 days. Effectiveness and safety parameters were measured at baseline, day 7, and day 14. Main Outcomes: BTP medication frequency on days 7 and 14, compared to baseline.

Results: Of the 141 patients screened, 114 received study drug and 98 completed the study. Compared to day 0, daily BTP medication frequency on day 14 decreased from 2.93 to 2.00 (p < 0.0001), daily BTP frequency decreased from 3.67 to 2.44 (p < 0.0001), and end-of-dose pain frequency decreased by 44 percent. Pain was controlled adequately during daytime and night-time. Pain intensity decreased by 11 percent as assessed using the Korean Brief Pain Inventory and by 17 percent as assessed using the numerical rating scale. About 61.2 percent patients and 60.2 percent physicians were satisfied with the treatment. Common adverse events, which occurred in 91.2 percent patients, were constipation, somnolence, and dizziness.

Conclusion: Once-daily OROS® hydromorphone is efficient in the reduction of cancer pain-related BTP episodes, including end-of-dose pain.


breakthrough pain, cancer, conversion ratio, OROS® hydromorphone, oxycodone

Full Text:



van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, et al.: Prevalence of pain in patients with cancer: A systematic review of the past 40 years. Ann Oncol. 2007; 18(9): 1437-1449.

Bennett D, Burton AW, Fishman S, et al.: Consensus panel recommendations for the assessment and management of breakthrough pain. Part I: Assessment. Pharm Ther. 2005; 30(5): 296-301.

World Health Organization (ed.): Cancer Pain Relief, 2nd ed. Geneva: WHO, 1986.

Liew E, Hui YL: A preliminary study of long-term epidural morphine for cancer pain via a subcutaneously implanted reservoir. Ma Zui Xue Za Zhi. 1989; 27(1): 5-12.

Dahan A: The importance of individual differences in response to opioid therapy. Therapy. 2009; 6(5): 2.

Cherny N, Ripamonti C, Pereira J, et al.: Strategies to manage the adverse effects of oral morphine: An evidence-based report. J Clin Oncol. 2001; 19(9): 2542-2554.

Sjogren P, Jensen NH, Jensen TS: Disappearance of morphine-induced hyperalgesia after discontinuing or substituting morphine with other opioid agonists. Pain. 1994; 59(2): 313-316.

Quigley C: Hydromorphone for acute and chronic pain. Cochrane Database Syst Rev. 2002(1): CD003447.

Palangio M, Northfelt DW, Portenoy RK, et al.: Dose conversion and titration with a novel, once-daily, OROS osmotic technology, extended-release hydromorphone formulation in the treatment of chronic malignant or nonmalignant pain. J Pain Symptom Manage. 2002; 23(5): 355-368.

Vallner JJ, Stewart JT, Kotzan JA, et al.: Pharmacokinetics and bioavailability of hydromorphone following intravenous and oral administration to human subjects. J Clin Pharmacol. 1981; 21(4): 152-156.

Drover DR, Angst MS, Valle M, et al.: Input characteristics and bioavailability after administration of immediate and a new extended-release formulation of hydromorphone in healthy volunteers. Anesthesiology. 2002; 97(4): 827-836.

Bruera E, Sloan P, Mount B, et al.: A randomized, double-blind, double-dummy, crossover trial comparing the safety and efficacy of oral sustained-release hydromorphone with immediate-release hydromorphone in patients with cancer pain. Canadian Palliative Care Clinical Trials Group. J Clin Oncol. 1996; 14(5): 1713-1717.

Wallace M, Rauck RL, Moulin D, et al.: Conversion from standard opioid therapy to once-daily oral extended-release hydromorphone in patients with chronic cancer pain. J Int Med Res. 2008; 36(2): 343-352.

Lawlor P, Turner K, Hanson J, et al.: Dose ratio between morphine and hydromorphone in patients with cancer pain: A retrospective study. Pain. 1997; 72(1-2): 79-85.

Wallace M, Rauck RL, Moulin D, et al.: Once-daily OROS hydromorphone for the management of chronic nonmalignant pain: A dose-conversion and titration study. Int J Clin Pract. 2007; 61(10): 1671-1676.

Yun YH, Mendoza TR, Heo DS, et al.: Development of a cancer pain assessment tool in Korea: A validation study of a Korean version of the brief pain inventory. Oncology. 2004; 66(6): 439-444.

Gogtay NJ: Principles of sample size calculation. Indian J Ophthalmol. 2010; 58(6): 517-518.

Oken MM, Creech RH, Tormey DC, et al.: Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982; 5(6): 649-655.

Moore KT, St-Fleur D, Marricco NC, et al.: Steady-state pharmacokinetics of extended-release hydromorphone (OROS hydromorphone): A randomized study in healthy volunteers. J Opioid Manag. 2010; 6(5): 351-358.

Angst MS, Drover DR, Lotsch J, et al.: Pharmacodynamics of orally administered sustained-release hydromorphone in humans. Anesthesiology. 2001; 94(1): 63-73.

Sathyan G, Xu E, Thipphawong J, et al.: Pharmacokinetic profile of a 24-hour controlled-release OROS formulation of hydromorphone in the presence and absence of food. BMC Clin Pharmacol. 2007; 7: 2.

Hanna M, Thipphawong J: A randomized, double-blind comparison of OROS(R) hydromorphone and controlled-release morphine for the control of chronic cancer pain. BMC Palliat Care. 2008; 7: 17.

Vissers KC, Besse K, Hans G, et al.: Opioid rotation in the management of chronic pain: Where is the evidence? Pain Pract. 2010; 10(2): 85-93.

Weinstein SM, Shi M, Buckley BJ, et al.: Multicenter, open-label, prospective evaluation of the conversion from previous opioid analgesics to extended-release hydromorphone hydrochloride administered every 24 hours to patients with persistent moderate to severe pain. Clin Ther. 2006; 28(1): 86-98.

Fujita K, Ando Y, Yamamoto W, et al.: Association of UGT2B7 and ABCB1 genotypes with morphine-induced adverse drug reactions in Japanese patients with cancer. Cancer Chemother Pharmacol. 2010; 65(2): 251-258.

Hong SH, Roh SY, Kim SY, et al.: Change in cancer pain management in Korea between 2001 and 2006: Results of two nationwide surveys. J Pain Symptom Manage. 2010 (in press).

Kim DY, Song HS, Ahn JS, et al.: The dosing frequency of sustained-release opioids and the prevalence of end-of-dose failure in cancer pain control: A Korean multicenter study. Support Care Cancer. 2010; 19(2): 297-301.



  • There are currently no refbacks.