Opioid rotation from oral morphine to oral oxycodone in cancer patients with intolerable adverse effects: an open-label trial.
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 approximately 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.
Narabayashi
Masaru
M
Department of Palliative Medicine, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama 350-1298, Japan. mnarabay@saitama-med.ac.jp.
Saijo
Yasuo
Y
Takenoshita
Seiichi
S
Chida
Masayuki
M
Shimoyama
Naohito
N
Miura
Takeshi
T
Tani
Kazuhiko
K
Nishimura
Kousuke
K
Onozawa
Yusuke
Y
Hosokawa
Toyoshi
T
Kamoto
Toshiyuki
T
Tsushima
Tomoyasu
T
D000284:Administration, Oral; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D003248:Constipation / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009019:Morphinans / Q000097:blood; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D009022:Morphine Derivatives / Q000097:blood; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000097:blood / Q000150:complications*; D010098:Oxycodone / Q000008:administration & dosage*; D010146:Pain / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications; D012894:Sleep Stages / Q000187:drug effects; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
D000701:Analgesics, Opioid; D009019:Morphinans; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine; C077256:noroxycodone; D010098:Oxycodone