To date, based on meta-analyses of clinical trials, no drug can be proposed as a gold standard to prevent or treat CIPN. Consequently, there is a strong discrepancy between the optimistic results of animal studies and the poor outcomes of clinical trials. Pain assessment in preclinical and clinical studies is probably not the best outcome measurement tool and all these studies should include composite outcomes including the full complexity of CIPN symptoms, such as positive symptoms (pain, paresthesia, and dysesthesia) and negative ones (numbness).

BACKGROUND: Anticoagulants are the only available compounds in the EU to control rat populations. Resistance to anticoagulant rodenticides (antivitamin K or AVK) is described and widespread across Europe. The present objective was to determine whether resistance was associated with an increased potential for bioaccumulation of AVK in the liver. Rats were selected from three major resistant genetically identified strains across Europe: Y139C (Germany), Y139F (France) and L120Q (United Kingdom). The rats were housed in individual cages and fed chlorophacinone wheat bait (50 mg kg −1 ). Animals were assigned to groups for euthanasia either on day 1, 4, 9 or 14 (resistant rats) or on days 1 and 4 (susceptible rats).RESULTS: Chlorophacinone accumulated from day 1 to day 4 in all strains (maximum 160 µg liver −1 ) and remained stable thereafter. There was no significant difference between strains. Extensive metabolism of chlorophacinone was also found, and was similar (in nature and proportion of metabolites) across strains (3 OH-metabolites identified). Only the survival time differed significantly (L120Q > Y139C = Y139F > susceptible).CONCLUSIONS: Accumulation of chlorophacinone occurs from day 1 to day 4, and an equilibrium is reached, suggesting rapid elimination. Resistant and susceptible rats accumulate chlorophacinone to the same extent and only differ in terms of survival times. Resistant rats may then be a threat for non-target species for prolonged periods of time.

IntroductionOxaliplatin remains the most widely used chemotherapeutic agent for treating advanced colorectal cancer but its efficacy is hampered by dose-limiting neurotoxicity manifested by a painful polyneuropathy. Oxaliplatin-induced peripheral neuropathy (OIPN) is characterised by acute and transient cold hyperaesthesia in the hours and days following oxaliplatin infusion (>90% of patients), but also by retarded chronic neuropathy due to the repetition of chemotherapy cycles (30–50% of patients). OIPN impairs the health-related quality of life (HRQOL) of patients and no preventive or curative strategies have as yet proven effective. A polyamine-reduced diet (PRD) has recently demonstrated its efficacy to prevent OIPN in animals without adverse effects.Methods and analysisThe NEUROXAPOL trial is a prospective, randomised, controlled, single-blind, monocentric and interventional study. This trial is aimed at evaluating the efficacy and feasibility of a PRD compared to a normal polyamine containing diet to prevent OIPN in patients treated by oxaliplatin-based chemotherapy. Patients (n=40 per group) will be randomly assigned to receive either a PRD or a normal diet before and during the chemotherapy regimen. The main objectives are to improve the cold pain thresholds, neuropathic pain symptoms, comorbidities (anxiety and depression) and HRQOL of patients. The primary end point is the assessment of cold pain thresholds 2 weeks after the third cycle of chemotherapy. The secondary end points are the evaluation of thermal pain thresholds, the grade of neuropathy, neuropathic pain, symptoms of anxiety and depression and HRQOL, until the 12th cycle of chemotherapy.Ethics and disseminationThe study was approved by an independent medical ethics committee 1 (CPP Sud Est 1, Saint Etienne, France) and registered by the competent French authority (ANSM, Saint Denis, France). The results will be disseminated in a peer-reviewed journal and presented at international congresses.Trial registration numberNCT01775449.