Does Riluzole reduce the incidence of chemotherapy-induced nerve injury in patients with colorectal cancer?

Phase 2

Completed

• Conditions: Colorectal cancer; Cancer - Bowel - Back passage (rectum) or large bowel (colon); Neurological - Other neurological disorders; Oxaliplatin-induced neurotoxicity

• Registration Number: ACTRN12611000514909
• Lead Sponsor: Prince of Wales Hospital/South Eastern Sydney Local Health Network

Brief Summary

Oxaliplatin has demonstrated superior activity as a first-line treatment in advanced colorectal cancer and as adjuvant treatment, and now represents a central component of colorectactal cancer treatment. However, the dose-limiting toxicity of oxaliplatin treatment is related to the development of peripheral neuropathy, present in up to 50% of patients at higher doses. Paraesthesia is the most commonly reported outcome representing a significant limitation to treatment, as end organ neurotoxicity and neuropathy may require discontinuation of effective therapy. Previous studies using nerve excitability techniques have provided insight into the pathophysiology of oxaliplatin induced neuropathy revealing prominent alterations in sodium channel function. The present study investigated the neuroprotective potential of riluzole, a drug currently used for the treatment of amyotrophic lateral sclerosis where it has demonstrated neuroprotective effects by blocking certain sodium channels. Fifty-two patients were recruited and randomised into either a treatment or control group. The treatment group received 50 mg of riluzole twice daily prior to oxaliplatin treatment until the end of the chemotherapy regime and the control group received matched lactose placebo. Neurophysiological and functional testing were conducted including the Total Neuropathy Score, nerve excitability measures and 9-hole pegboard test. A major limitation of this study was that the recruitment target was not reached and accordingly, a post-hoc repeated measures analyses was employed to address the limited sample size. The results indicated there was no benefit of riluzole on the development of neuropathy during chemotherapy treatment and up to 12 weeks post-treatment. Although the current study was underpowered, the authors observed no indication that would suggest further investigation is warranted.

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-05-18
• Study Completion: 2016-09-19
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

1. Receiving oxaliplatin chemotherapy.
2. 18-80 years of age.
3. Able to provide written informed consent.
4. Histological or cytological confirmation of colorectal cancer.

Exclusion Criteria

1. Baseline clinical and nerve conduction evidence of pre-existing neuropathy.
2. Past history of neurotoxic chemotherapy treatment.
3. Concurrent use of anticonvulsant medications that modulate axonal Na+ conductances (carbamazepine, topiramate, phenytoin).
4. Evidence of baseline elevation of hepatic transaminases (greater than 3 times the upper limit of normal) on liver function testing.
5. Administration of another investigational drug within 30 days prior to randomisation.
6. A history of severe hypersensitivity reactions to riluzole or any of the tablet components
7. Significant neurological or psychiatric disorders.
8. Pregnancy or lactation. Contraception is required in pre-menopausal female patients.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To assess whether treatment with riluzole results in a reduction in the development of chronic neuropathy and neuropathic symptoms<br><br>The severity of neuropathy will be assessed using the Total Neuropathy Score (TNS). This will be used to evaluate neuropathy in a number of different categories; sensory neuropathic symptoms, examination findings and nerve conduction results.[Assessed at 6 monthly intervals following randomisation for 2 years]