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

Contemp Clin Trials. 2015 Mar:41:146-51. doi: 10.1016/j.cct.2015.01.012. Epub 2015 Jan 28.

Abstract

Background: Anti-cancer chemotherapy often induces peripheral neuropathy and consequent cognitive and quality of life impairment. Guidelines recommend antiepileptics or antidepressants but their efficacy is limited.Dextromethorphan, a N-methyl-D-aspartate receptor antagonist, has shown its efficacy in painful diabetic neuropathy and in post-operative pain but has not been studied in chemotherapy-induced peripheral neuropathy. This clinical trial evaluates the effect of dextromethorphan on pain, cognition and quality of life in patients who suffer from neuropathic pain induced by chemotherapy for breast cancer. It also assesses the impact of dextromethorphan genetic polymorphism on analgesia.

Methods and design: This trial is a randomized, placebo-controlled, double-blind clinical study in two parallel groups (NCT02271893). It includes 40 breast cancer patients suffering from chemotherapy-induced peripheral neuropathy. They are randomly allocated to dextromethorphan (maximal dose 90 mg/day) or placebo for 4 weeks. The primary endpoint is pain intensity measured after 4 weeks of treatment on a (0-10) Numeric Pain Rating Scale. Secondary outcomes include assessment of neuropathic pain, cognitive function, anxiety/depression, sleep and quality of life. Data analysis is performed using mixed models and the tests are two-sided, with a type I error set at α=0.05.

Discussion: Considering the poor efficacy of available drugs in chemotherapy-induced neuropathic pain, dextromethorphan may be a valuable therapeutic option. Pharmacogenetics may provide predictive factors of dextromethorphan response in patients suffering from breast cancer.

Keywords: Breast cancer; Cognition; Dextromethorphan; Genetic polymorphism; Quality of life.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Antineoplastic Agents / adverse effects*
  • Anxiety / psychology
  • Breast Neoplasms / drug therapy*
  • Cognition
  • Cytochrome P-450 CYP2D6 / genetics
  • Cytochrome P-450 CYP3A / genetics
  • Depression / psychology
  • Dextromethorphan / therapeutic use*
  • Double-Blind Method
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Female
  • Humans
  • Neuralgia / chemically induced
  • Neuralgia / drug therapy*
  • Neuralgia / psychology
  • Neuropsychological Tests
  • Pain Measurement
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / drug therapy*
  • Peripheral Nervous System Diseases / psychology
  • Pharmacogenetics
  • Polymorphism, Genetic
  • Quality of Life

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Antineoplastic Agents
  • Excitatory Amino Acid Antagonists
  • Dextromethorphan
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human

Associated data

  • ClinicalTrials.gov/NCT02271893