Update on targeted treatments for painful neuropathy


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Session type:

Marie Fallon1
1IGMM Edinburgh Cancer Research Centre

Abstract

In an attempt to alleviate painful chemotherapy induced peripheral neuropathy (CIPN), clinicians and patients try various therapeutic interventions, despite the limited evidence to support efficacy of these treatments. The rationale for such use is mostly based on the evidence for the treatment options in non-CIPN peripheral neuropathy syndromes, as this area is more robustly studied than CIPN. It may be reasonable to extrapolate data in this way, however increasingly it is thought that underlying neurobiological changes dictate analgesic response rather than specific aetiology.

Antidepressants: Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) with known efficacy in the treatment of various pain syndromes and there are three randomised controlled trials (RCTs) with positive results at 60mg per day in diabetic peripheral neuropathic pain. In CIPN, a pilot trial suggested some benefit for duloxetine. A 231 patient phase III RCT evaluated duloxetine at 60mg per day for the treatment of painful CIPN attributed to taxane or oxaliplatin therapy. Patients who received duloxetine had a larger average decrease in pain score and sub-group analysis supported the most benefit in patients who had received oxaliplatin with little or no benefit in patients who had received paclitaxel. There is low level evidence for the use of venlafaxine. An RCT with nortriptyline in a crossover design involving 51 patients with cisplatin induced peripheral neuropathy showed no significant effect.

Antiepileptics: The gabapentinoids - There are limited supporting data for the use of gabapentin to treat CIPN; furthermore a phase III randomised double-blind crossover trial with 115 patients failed to demonstrate any suggestion of benefit. There is low-level evidence for pregabalin with a single-blind study.

Opioids: Limited data are available for the use of opioids in the treatment of CIPN, however open studies suggest potential benefit.

Topical agents: Topical amitriptyline, ketamine +/- baclofen - an RCT involving 208 patients with CIPN from a variety of chemotherapeutic agents showed a greater improvement in the amitriptyline, ketamine, baclofen arm particularly in relation to sensory symptoms. Topical menthol - translational research with the TRPM8 agonist, menthol, in CIPN shows potential promised but needs further evaluation. High dose topical capsaicin patches (8%) are licensed for peripheral neuropathic pain and, with case series of patients with CIPN, are showing promise, however appropriately designed studies are awaited.

Other agents: Other potential treatments include acetyl-L-carnitine (ALC), acupuncture and neurostimulation.

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