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Neu-horizons: neuroprotection and therapeutic use of riluzole for the prevention of oxaliplatin-induced neuropathy—a randomised controlled trial

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Abstract

Trial design

Peripheral neuropathy is a commonly reported adverse effect of oxaliplatin treatment, representing a significant limitation which may require discontinuation of effective therapy. The present study investigated the neuroprotective potential of riluzole in patients undergoing oxaliplatin treatment in a randomised-controlled trial comparing riluzole and placebo-control.

Methods

Fifty-two patients (17 females, 58.1 ± 12.7 years) receiving oxaliplatin treatment were randomised into either a treatment (50 mg riluzole) or lactose placebo group. The primary outcome measure was the total neuropathy score-reduced (TNSr). Secondary outcome measures include nerve excitability measures, 9-hole pegboard and FACT-GOG NTX questionnaire. Patients were assessed at baseline, pre-cycle 10 or 12, 4-week and 12-week post-treatment.

Results

Both the treatment and placebo groups developed objective and patient reported evidence of neurotoxicity over the course of oxaliplatin treatment, although there were no significant differences across any parameters between the two groups. However, across follow-up assessments, the treatment group experienced greater neuropathy, represented by a higher TNSr score at 4-week post-chemotherapy of 8.3 ± 2.7 compared with 4.6 ± 3.6 (p = 0.032) which was sustained at 12-week post-treatment (p = 0.089). Similarly, patients in the treatment group reported worse symptoms with a FACT-GOG NTX score of 37.4 ± 10.2 compared with 43.3 ± 7.4 (p = 0.02) in the placebo group at 4-week post-treatment.

Conclusion

This study is the first to provide an objective clinical investigation of riluzole in oxaliplatin-induced peripheral neuropathy employing both functional and neurophysiological measures. Although the recruitment target was not reached, the results do not show any benefit of riluzole in minimising neuropathy and may suggest that riluzole worsens neuropathy associated with oxaliplatin treatment.

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Funding

This study was supported by a National Health and Medical Research Council of Australia (NHMRC) Project Grant (#1007628) and a Cancer Institute NSW Program Grant (14/TPG/1–05). SBP is supported by a NHMRC Career Development Fellowship (#1148595). MCK is supported by a NHMRC Practitioner Fellowship (#1156093); and by ForeFront, a large collaborative research group dedicated to the study of neurodegenerative diseases and funded by the National Health and Medical Research Council of Australia Program Grant (#1132524).

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Authors and Affiliations

  1. Prince of Wales Clinical School, University of New South Wales, Sydney, Australia

    Terry Trinh, Jenna Murray, Hannah Pickering, David Goldstein & Arun V. Krishnan

  2. Brain and Mind Centre, University of Sydney, Sydney, Australia

    Susanna B. Park, Cindy S.-Y. Lin & Matthew C. Kiernan

  3. National Health and Medical Research Centre Clinical Trials Centre, University of Sydney, Sydney, Australia

    Andrew Martin

  4. Department of Medical Oncology, Prince of Wales Hospital, Randwick, Sydney, Australia

    Michael Friedlander & David Goldstein

  5. Department of Neurological Sciences, Prince of Wales Hospital, Level 2 High Street, Randwick, Sydney, NSW, 2031, Australia

    Arun V. Krishnan

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  1. Terry Trinh
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Correspondence to Arun V. Krishnan.

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Trinh, T., Park, S.B., Murray, J. et al. Neu-horizons: neuroprotection and therapeutic use of riluzole for the prevention of oxaliplatin-induced neuropathy—a randomised controlled trial. Support Care Cancer 29, 1103–1110 (2021). https://doi.org/10.1007/s00520-020-05591-x

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