Comparison of sustained-release morphine with sustained-release oxycodone in advanced cancer patients

G R Lauretti, G M Oliveira, N L Pereira, G R Lauretti, G M Oliveira, N L Pereira

Abstract

The antinociceptive effect of morphine and oxycodone is mediated preferentially at micro and kappa receptors, respectively. The aim of this study was to evaluate the analgesic profile of the combination of morphine and oxycodone in cancer pain, compared to the standard administration of morphine alone. Controlled-release formulations of oxycodone (CRO) and morphine (CRM) were compared in 26 patients. The study started with an open-label, randomised titration phase to achieve stable pain control for 7 days, followed by a double-blind, randomised crossover phase in two periods, 14 days each. At any point, patients were allowed to use oral immediate-release morphine (IRM) as needed, in order to keep visual analogue scale < or =4. Pain, satisfaction, adverse effects and number of daily rescue morphine tablets were assessed. A total of 22 patients were evaluated. The weekly upload consumption ratio in morphine/oxycodone was 1 : 1.8 (1.80, 1.83, 1.76, 1.84). The weekly IRM consumption was higher in patients having CRM compared to patients having CRO (ratio morphine/oxycodone: 1.6, 1.6, 1.6, 1.7) (P<0.05). Patients receiving oxycodone complained of less nausea and vomiting. The rescue morphine analgesic consumption was 38% higher in patients receiving only morphine, compared to patients receiving both morphine and oxycodone. The results suggest that the combination of morphine/oxycodone (opioids with differential preferential sites of action) can be a useful alternative to morphine alone, resulting in a better analgesia profile and less emesis.

Figures

Figure 1
Figure 1
Mean final weekly doses of CRM and CRO (mg) are described in bars. The lines over the bars indicate the standard deviation of the mean. The consumption ratio of CRM/CRO was 1.80, 1.83, 1.76 and 1.84, during the study period, set by the pharmaceutical.
Figure 2
Figure 2
Mean daily number of rescue analgesic IRM (10 mg) at the end of each week. The weekly IRM consumption was higher in patients having CRM compared to patients having CRO (P<0.05). Morphine values: 2(0–2.5); 2(0–3); 2(0–2); 2(1–3). Oxycodone values: 1(0–3); 0.5(0–2); 1(0–2); 1(0–1.5).

References

    1. Cann C, Curran J, Milner T, Ho B (2002) Unwanted effects of morphine-6-glucoronide and morphine. Anaesthesia 57: 1200–1203
    1. Davis MP, Varga J, Dickerson D, Walsh D, LeGrand SB, Lagman R (2003) Normal-release and controlled-release oxycodone: pharmacokinetics, pharmacodynamics, and controversy. Support Care Cancer 11: 84–92
    1. Duttaroy A, Yoburn BC (1995) The effect of intrinsic efficacy on opioid tolerance. Anesthesiology 82: 1226–1236
    1. Enting RH, van der Rijt CC, Wilms EB, Lieverse PJ, de Wit R, Smith PA (2001) Treatment of pain in cancer with systematically administered opioids. Ned Tijdschr Geneeskd 19: 950–954
    1. Freye E, Latasch L (2003) Development of opioid tolerance – molecular mechanisms and clinical consequences. Anasthesiol Intensivmed Notfallmed Schmerzther 38: 14–26
    1. Hanks GW, Conno F, Cherny N, Hanna M, Kalso E, McQuay HJ, Mercadante S, Meynadier J, Poulain P, Ripamonti C, Radbruch L, Casas JR, Sawe J, Twycross RG, Ventafridda V, Expert Working Group of the Research Network of the European Association for Palliative Care (2001) Morphine and alternative opioids in cancer pain: the EAPC recommendations. Br J Cancer 84: 587–593
    1. Heiskanen T, Kalso E (1997) Controlled-release oxycodone and morphine in cancer related pain. Pain 73: 37–45
    1. Heiskanen TE, Ruismaki PM, Seppala TA, Kalso EA (2000) Morphine or oxycodone in cancer pain? Acta Oncol 39: 941–947
    1. Klepstad P, Kassa S, Jystad A, Hvai B, Borchgrevink PC (2003) Immediate- or sustained-release morphine for dose finding during start of morphine to cancer patients: a randomized, double-blind trial. Pain 101: 193–198
    1. Moore RA, Gavaghan D, Tramer MR, Collins SL, McQuay HJ (1998) Size is everything – large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects. Pain 78(3): 209–216
    1. Mucci-LoRusso P, Berman BS, Silberstein PT, Citron ML, Bressler L, Weinstein SM, Kaiko RF, Buckley BJ, Reder RF (1998) Controlled release oxycodone compared with controlled-release morphine in the treatment of cancer pain: a randomized, double-blind, parallel-group study. Eur J Pain 2: 239–249
    1. Narita M, Khotib J, Suzuki M, Ozaki S, Yajima Y, Suzuki T (2003) Heterologous mu-opioid receptor adaptation by repeated stimulation of kappa-opioid receptor: up-regulation of G-protein activation and antinociception. J Neurochem 85(5): 1171–1179
    1. Nielsen CK, Ross FB, Smith MT (2000) Incomplete, asymmetric, and route-dependent cross-tolerance between oxycodone and morphine in the Dark Agouti rat. J Pharmacol Exp Ther 295: 91–99
    1. Poyhia R, Vainio A, Kalso E (1993) A review of oxycodone's clinical pharmacokinetics and pharmacodynamics. J Pain Symptom Manage 8: 63–67
    1. Ripamonti C, Dickerson ED (2001) Strategies for the treatment of cancer pain in the new millennium. Drugs 61: 955–977
    1. Ross FB, Smith MT (1997) The intrinsic antinociceptive effects of oxycodone appear to be kappa-opioid receptor mediated. Pain 73: 151–157
    1. Ross FB, Wallis SC, Smith MT (2000) Co-administration of sub-antinociceptive doses of oxycodone and morphine produces marked antinociceptive synergy with reduced CNS side effects. Pain 84: 421–428
    1. Zhukovsky DS, Walsh D, Doona M (1999) The relative potency between high dose oral oxycodone and intravenous morphine: a case illustration. J Pain Symptom Manage 18: 53–55

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi