Study protocol: fish oil supplement in prevention of oxaliplatin-induced peripheral neuropathy in adjuvant colorectal cancer patients - a randomized controlled trial. (OxaNeuro).

BACKGROUND: Oxaliplatin-induced peripheral neuropathy (OIPN) in general and painful OIPN in particular is a debilitating late effect that severely affects cancer survivors' quality of life and causes premature cessation of potentially lifesaving treatment. No preventive treatments and no effective treatment for chronic OIPN exist despite many attempts. One of several suggested mechanisms includes neuroinflammation as a contributing factor to OIPN. Fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFAs) are precursors to specialized proresolving mediators that mediate the resolution of inflammation. Our primary hypothesis is that a high supplementation of n-3 LCPUFAs will lower the prevalence and severity of OIPN. METHODS: The OxaNeuro project is an investigator-initiated, multicenter, double-blinded, randomized, placebo-controlled clinical study. We will include 120 patients eligible to receive adjuvant oxaliplatin after colorectal cancer surgery. Patients will receive fish oil capsules containing n-3 LCPUFAs or corn oil daily for 8 months. The primary endpoint is the prevalence of OIPN at 8 months defined as relevant symptoms, including one of the following: abnormal nerve conduction screening, abnormal vibration threshold test, abnormal skin biopsy, or abnormal pinprick test. Additional endpoints include the intensity and severity of OIPN-related neuropathic pain, patient-reported OIPN symptoms, quality of life, mental health symptoms, body composition, and cognitive evaluation. Furthermore, we will evaluate inflammatory biomarkers in blood samples and skin biopsies, including the potential OIPN biomarker neurofilament light protein (NfL) which will be measured before each cycle of chemotherapy. DISCUSSION: If readily available fish oil supplementation alleviates OIPN prevalence and severity, it will significantly improve the lives of both cancer survivors and palliative cancer patients receiving oxaliplatin; it will improve their quality of life, optimize chemotherapeutic treatment plans by lowering the need for dose reduction or premature cessation, and potentially increase survival. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT05404230 Protocol version: 1.2, April 25th. 2023.

Cold aggravates abnormal excitability of motor axons in oxaliplatin-treated patients.

INTRODUCTION: Cold allodynia is often seen in the acute phase of oxaliplatin treatment, but the underlying pathophysiology remains unclear. METHODS: Patients scheduled for adjuvant oxaliplatin for colorectal cancer were examined with quantitative sensory testing and nerve excitability tests at baseline and after the second or third oxaliplatin cycle at different skin temperatures. RESULTS: Seven patients were eligible for examination. All patients felt evoked pain and tingling when touching something cold after oxaliplatin infusion. Oxaliplatin decreased motor nerve superexcitability (P < .001), increased relative refractory period (P = .011), and caused neuromyotonia-like after-activity. Cooling exacerbated these changes and prolonged the accommodation half-time. DISCUSSION: The findings suggest that a combined effect of oxaliplatin and cooling facilitates nerve excitability changes and neuromyotonia-like after-activity in peripheral nerve axons. A possible mechanism is the slowing in gating of voltage-dependent fast sodium and slow potassium channels, which results in symptoms of cold allodynia.