Rapid Fire Oral Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2026

Can Oxaliplatin neurotoxicity be reduced with ibudilast in people with colorectal cancer (CRC)? OXTOX – a phase II placebo-controlled randomised trial   (146170)

Haryana Dhillon 1 , David Espinoza 2 , Mason Aberoumand 2 , Christina Teng 3 , Lorraine Chantrill 4 , Matt Wong 3 , Gavin Marx 5 , Prunella Blinman 6 , Rachel Wong 7 8 , Deme Karikios 9 , Connie Diakos 10 , Erin Moth 11 , Peter Fox 12 , Stephen Begbie 13 , Christopher Steer 14 , Bruce Cheek 15 , Gemma Collett 15 , Shaun Kirsten 1 , Susanna Park 16 , Martin Stockler 2 , Janette Vardy 16 17
  1. Psycho-Oncology Cooperative Research Group, School of Psychology, University of Sydney, Sydney
  2. Sydney Clinical Trials Centre, University of Sydney , Sydney, NSW, Australia
  3. Gosford Hospital, Gosford, NSW
  4. Illawarra Cancer Care Centre, Wollongong Hospital, Wollongong
  5. Sydney Adventist Hospital, Wahroonga, NSW
  6. Concord Cancer Centre, Concord Repatriation General Hospital, Concord, NSW
  7. Eastern Health Clinical School, Monash University , Box Hill , Victoria, Australia
  8. Department of Medical Oncology, Eastern Health , Box Hill , Victoria , Australia
  9. Nepean Cancer and Wellness Centre, Nepean Hospital, Penrith
  10. Royal North Shore Hospital, St Leonards, NSW, Australia
  11. Medical Oncology, Macquarie University Hospital, Macquarie
  12. Central West Cancer Care Centre, Orange Hospital, Orange, NSW
  13. Port Macquarie Base Hospital, Port Macquarie, NSW, Australia
  14. Border Medical Oncology Research Unit , Albury Wodonga Regional Cancer Centre , Albury , NSW, Australia
  15. GI Cancer Trials, Sydney, NSW
  16. Faculty of Medicine and Health, The University of Sydney , Sydney
  17. Australian Research Centre for Cancer Survivorship, University of New South Wales, Sydney, NSW, Australia

Background
Chemotherapy-induced peripheral neuropathy (CIPN) is the main dose-limiting factor for oxaliplatin, affecting quality-of-life and function. Severity of acute neurotoxicity (paraesthesias or dysesthesias) predicts CIPN. We evaluated whether ibudilast (an oral phosphodiesterase inhibitor) could reduce the severity of acute neurotoxicity and CIPN.

Methods
A randomised phase 2 placebo-controlled trial evaluating ibudilast 30mg PO bd, started 2 days before oxaliplatin, in participants treated with FOLFOX or CAPOX for early or metastatic CRC. Primary outcome: severity of acute neurotoxicity (Oxaliplatin Acute Symptom Questionnaire [OASQ] score, higher score worse). Key secondary outcomes: CIPN, adverse events. Comparisons are ibudilast vs placebo, with 2-sided p-values and 95% CI.

Results
We recruited 100 patients at 11 sites, November 2021 to July 2025: 51 assigned ibudilast, 49 placebo. Median age 62 (IQR 49-70); 57 early CRC (3-mo OX planned in 17, 6-mo in 40), 43 metastatic CRC.
Acute neurotoxicity: Mean OASQ score day 3 of week 4 CAPOX and week 5 FOLFOX: 7.1 vs 6.6, (difference 0.5, 95%CI -2.8, 3.9, p=0.8). Scores worsened over time but were similar between groups.
CIPN: FACT-GOG-Ntx-total, Ntx-subscale, Total Neuropathy Scores, Grooved Pegboard, worsened over time but were similar between groups. Ntx-subscale scores (lower score worse) 6-months after completing oxaliplatin were 32.4 vs 32.6; mixed model difference over time -0.06, p=0.966.
Mean number of oxaliplatin cycles: 7 in both adjuvant and metastatic settings. Median time to oxaliplatin discontinuation: ibudilast 3.7 vs placebo 4.8, p=0.36. Only 11% completed 3-months of oxaliplatin without dose modification: 3 (5.9%) vs 8 (16.3%).
Proportion of participants adhering to study treatment: ibudilast 68% vs placebo 73%. The frequency and severity of adverse events appeared similar between groups.

Conclusions
We found insufficient evidence to warrant further study of ibudilast for oxaliplatin-induced neuropathy. It was feasible to run a high-quality, multi-site, placebo-controlled, randomised trial with comprehensive assessment of neurotoxicity.