Japanese Journal of Clinical Oncology Advance Access originally published online on March 7, 2008
Japanese Journal of Clinical Oncology 2008 38(4):296-304; doi:10.1093/jjco/hyn010
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© The Author (2008). Published by Oxford University Press. All rights reserved
Opioid Rotation from Oral Morphine to Oral Oxycodone in Cancer Patients with Intolerable Adverse Effects: An Open-Label Trial
1 Department of Palliative Medicine, Saitama Medical University International Medical Center, Saitama
2 Department of Molecular Medicine, Tohoku University Graduate School of Medicine, Sendai
3 Department of Surgery II, Fukushima Medical University School of Medicine, Fukushima
4 Department of Chest Surgery, Ota Nishinouchi Hospital, Fukushima
5 Department of Anesthesiology and Palliative Medicine, National Cancer Center Hospital, Tokyo
6 Department of Urology, Kanagawa Cancer Center, Kanagawa
7 Department of Palliative Care, Fukui-ken Saiseikai Hospital, Fukui
8 Palliative Care Unit, Gifu Central Hospital, Gifu
9 Division of Gastrointestinal Oncology and Endoscopy, Shizuoka Cancer Center, Shizuoka
10 Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto
11 Department of Urology, Kyoto University, Graduate School of Medicine, Kyoto
12 Department of Urology, NHO Okayama Medical Center, Okayama, Japan
For reprints and all correspondence: Masaru Narabayashi, Department of Palliative Medicine, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama 350-1298, Japan. E-mail: mnarabay{at}saitama-med.ac.jp
Received September 14, 2007; accepted February 2, 2008
Objective: We prospectively investigated the efficacy of opioid rotation from oral morphine to oral oxycodone in cancer patients who had difficulty in continuing oral morphine treatment because of inadequate analgesia and/or intolerable side effects.
Methods: Twenty-seven patients were enrolled and 25 were evaluated. The rate of patients who achieved adequate pain control, which provided an indication of treatment success, was evaluated as primary endpoint. The acceptability and pharmacokinetics of oxycodone were evaluated in addition to the assessment of analgesic efficacy and safety during the study period.
Results: In spite of intense pain, the morphine daily dose could not be increased in most patients before the study because of intolerable side effects. However, switching to oral oxycodone allowed 
1.7-fold increase as morphine equivalent dose. Consequently, 84.0% (21/25) of patients achieved adequate pain control. By the end of the study, all patients except one had tolerated the morphine-induced intolerable side effects (i.e. nausea, vomiting, constipation, drowsiness). Common side effects (>10%) that occurred during the study were typically known for strong opioid analgesics, and most were mild to moderate in severity. A significant negative correlation between creatinine clearance (CCr) value and the trough concentrations of the morphine metabolites was observed. On the other hand, no significant correlation was found between CCr value and the pharmacokinetic parameters of oxycodone or its metabolites.
Conclusions: For patients who had difficulty in continuing oral morphine treatment, regardless of renal function, opioid rotation to oral oxycodone may be an effective approach to alleviate intolerable side effects and pain.
Key Words: opioid rotation • morphine • oxycodone • cancer pain • pharmacokinetics
Other members are listed in the Appendix.