Methadone against cancer: Lost in translation

Abstract

Recently, the opioid analgesic D,L-methadone has gained much attention as a potential antineoplastic compound, considerably triggered through lay press and media. In consequence, physicians and pharmacists are currently confronted with numerous patients willing to use D,L-methadone against their malignancies. Well-performed in vitro and in vivo models have in fact shown pro-apoptotic effects of D,L-methadone or other opioids, but also proliferation-stimulating properties. Moreover, the mechanisms of proposed opioid-stimulated apoptosis are incompletely described or contradicting. Finally, the receptors mostly responsible for induction of apoptosis by D,L-methadone remain unclear as contributions of both µ-opioid receptors, Fas cell death receptors, toll-like receptors, N-Methyl-D-aspartate receptors, and opioid growth factor receptors were suggested. Such ambiguity prevents rational application of D,L-methadone or patient stratification to enhance beneficial antineoplastic effects.

From a clinical point of view, D,L-methadone and other opioids might in fact prolong survival, but such effects likely originate from their analgesic and neuro-psychotropic properties and thus improvements of quality of life. Crucial obstacles to the administration of D,L-methadone are incomplete knowledge about its systemic disposition, highly variable pharmacokinetics, profound drug-drug- or drug-disease interaction, and QT-prolongation potential.

This article summarizes and rates the pharmacological basis of D,L-methadone as an antineoplastic agent and puts its administration in clinical oncology into perspective. Despite enthralling experimental findings about D,L-methadone-mediated apoptosis in cancerous cells or tissues, clinicians should realize the current lack of evidence for the use of D,L-methadone as an antineoplastic agent. Its administration against cancer pain is however tenable, albeit restricted to certain clinical situations. This article is protected by copyright. All rights reserved.

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