Rationale and design of a randomized double-blind clinical trial in breast cancer: Dextromethorphan in chemotherapy-induced peripheral neuropathy

Martin, Elodie; Morel, Véronique; Joly, Dominique; Villatte, Christine; Delage, Noémie; Dubray, Claude; Pereira, Bruno; Pickering, Gisèle

doi:10.1016/j.cct.2015.01.012

Cited by 9 publications

(3 citation statements)

References 52 publications

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“…The learning effect during the reaction time test, illustrated by a modest decrease of reaction time after each repeated test, was amplified with placebo compared to dextromethorphan (P < 0.02). Such a defect in learning with dextromethorphan could be explained by the impairment of learning and memorization mediated by antagonists of the NMDA receptor, 12 rather than by a sedative effect that was similarly little reported in both groups. This specific impact of dextromethorphan on new learning would benefit from exploration in future studies with other specific cognitive tests like Paired Associates Learning (Cambridge Neuropsychological Test Automated Battery).…”

Section: Dextromethorphan Effects On Hyperalgesiamentioning

confidence: 93%

“…A preclinical study in a spinal nerve ligation animal model showed that postsurgical dextromethorphan administration induced a significant decrease of allodynia and hyperalgesia while preserving mobility and cognition in the Y-maze test. 6 These positive findings in animals and in some clinical studies showing neuropathic pain alleviation after trauma 7,8 and diabetes, 9 although not universal, 10,11 triggered an ongoing clinical trial (NCT02271893) 12 in patients with refractory postsurgery neuropathic pain and central pain sensitization. To complement this translational approach, human experimental pain models may mimic some neuropathic pain characteristics and central pain sensitization, and help to understand the pharmacology of dextromethorphan.…”

Section: Dextromethorphan Effects On Hyperalgesiamentioning

confidence: 99%

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Dextromethorphan Analgesia in a Human Experimental Model of Hyperalgesia

et al. 2019

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Background: Central pain sensitization is often refractory to drug treatment. Dextromethorphan, an N-methyl-d-aspartate receptor antagonist, is antihyperalgesic in preclinical pain models. The hypothesis is that dextromethorphan is also antihyperalgesic in humans. Methods: This randomized, double-blind, placebo-controlled, crossover study explores the antihyperalgesic effect of single and repeated 30-mg dose of oral dextromethorphan in 20 volunteers, using the freeze-injury pain model. This model leads to development of primary and secondary hyperalgesia, which develops away from the site of injury and is associated with central sensitization and activation of N-methyl-d-aspartate receptor in the spinal cord. The primary outcome was antihyperalgesia calculated with the area under the curve of the percentage change in mechanical pain threshold (electronic von Frey) on the area of secondary hyperalgesia. The secondary outcomes were mechanical pain threshold on the area of primary hyperalgesia and cognitive (reaction time) effect. Results: Single 30-mg results are reported. Antihyperalgesia (% • min) is significantly higher on the area of secondary hyperalgesia with dextromethorphan than placebo (median [interquartile range]: 3,029 [746; 6,195] vs. 710 [-3,248; 4,439], P = 0.009, Hedge's g = 0.8, 95% CI [0.1; 1.4]). On primary hyperalgesia area, mechanical pain threshold 2 h after drug intake is significantly higher with dextromethorphan (P = 0.011, Hedge's g = 0.63, 95% CI [0.01; 1.25]). No difference in antinociception is observed after thermal painful stimuli on healthy skin between groups. Reaction time (ms) is shorter with placebo than with dextromethorphan (median [interquartile range]: 21.6 [-37.4; 0.1] vs.-1.2 [-24.3; 15.4], P = 0.015, Hedge's g = 0.75, 95% CI [0.12; 1.39]). Nonserious adverse events occurrence (15%, 3 of 20 volunteers) was similar in both groups. conclusions: This study shows that low-dose (30-mg) dextromethorphan is antihyperalgesic in humans on the areas of primary and secondary hyperalgesia and reverses peripheral and central neuronal sensitization. Because dextromethorphan had no intrinsic antinociceptive effect in acute pain on healthy skin, N-methyl-d-aspartate receptor may need to be sensitized by pain for dextromethorphan to be effective.

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Section: Dextromethorphan Effects On Hyperalgesiamentioning

confidence: 93%

Section: Dextromethorphan Effects On Hyperalgesiamentioning

confidence: 99%

Dextromethorphan Analgesia in a Human Experimental Model of Hyperalgesia

et al. 2019

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“…However, anticancer chemotherapy often induces peripheral neuropathy and as a consequence cognitive decline and finally quality of life is impaired. Commonly anti-epileptics or anti-depressants are recommended, but their efficacy is not satisfactory [7]. Going forward, whether anti-cancer therapy can reverse AD remains to be scientifically proven.…”

Section: Introductionmentioning

confidence: 99%

The Emerging Role of Anticancer-Drugs-Bexarotene in a Clinical Trial of Alzheimer’s Dementia

Pathakp¹

2017

CTOIJ

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Background: Cancer is a disease which affects the elderly, just like Alzheimer's disease (AD) which is also a common disease affecting older people. Most of the symptoms are related with both these diseases, therefore there may be therapeutic link between anticancer drugs and AD. Objective:To synthesize the studies aimed at therapeutic links between Alzheimer's disease and anticancer drugs (Bexarotene). Design:To identify potential new treatment possibilities we applied the systematic searches of key electronic databases. The inclusion criteria were; a. Studies aimed at improving cancer and anticancer therapies with human model. b. Peer-reviewed and written in English without any searching limitation on the basis of published date. c. Studies of drugs related to cancer treatment that was relevant to AD. d. We did not include the clinical news, case report and animal trial studies.Results: After filtering titles, abstract, references published in English into one study that has been condensed into one volume of literature. There is very hard to find studies aimed at therapeutic links between Alzheimer's disease and Anti-cancer drugs in human model. However, sufficient studies are conducted with animal model (mice) and indicating the positive benefits to the AD patients. Bexarotene is useful for the reduction of cholesterol, loss of function associated with APOE ε4, peripheral thyroid hormone metabolism and athyreotic and amyloid beta that is a key cofactor of Alzheimer's disease. Also, Bexarotene has been shown to restore cognitive functions. Conclusion:This review discusses the emerging role of anticancer-drugs-Bexarotene in a clinical trial of Alzheimer's dementia with the support of animal model successful results and their effectiveness and will be a significant drug in the coming decades.

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