Prevention of oxaliplatin-induced peripheral neuropathy by a polyamine-reduced diet-NEUROXAPOL: protocol of a prospective, randomised, controlled, single-blind and monocentric trial

David Balayssac, Jérémy Ferrier, Bruno Pereira, Brigitte Gillet, Caroline Pétorin, Julie Vein, Frédéric Libert, Alain Eschalier, Denis Pezet, David Balayssac, Jérémy Ferrier, Bruno Pereira, Brigitte Gillet, Caroline Pétorin, Julie Vein, Frédéric Libert, Alain Eschalier, Denis Pezet

Abstract

Introduction: Oxaliplatin 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 analysis: The 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 dissemination: The 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 number: NCT01775449.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

Figure 1
Figure 1
Administration scheme of polyamine-reduced diet according to the time course of chemotherapy cycle.

References

    1. Nordlinger B, Sorbye H, Glimelius B et al. . Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol 2013;14:1208–15. 10.1016/S1470-2045(13)70447-9
    1. Beijers AJM, Mols F, Vreugdenhil G. A systematic review on chronic oxaliplatin-induced peripheral neuropathy and the relation with oxaliplatin administration. Support Care Cancer 2014;22:1999–2007. 10.1007/s00520-014-2242-z
    1. Balayssac D, Ferrier J, Descoeur J et al. . Chemotherapy-induced peripheral neuropathies: from clinical relevance to preclinical evidence. Expert Opin Drug Saf 2011;10:407–17. 10.1517/14740338.2011.543417
    1. Tofthagen C. Surviving chemotherapy for colon cancer and living with the consequences. J Palliat Med 2010;13:1389–91. 10.1089/jpm.2010.0124
    1. Yothers G, O'Connell MJ, Allegra CJ et al. . Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol 2011;29:3768–74. 10.1200/JCO.2011.36.4539
    1. Attal N, Bouhassira D, Gautron M et al. . Thermal hyperalgesia as a marker of oxaliplatin neurotoxicity: a prospective quantified sensory assessment study. Pain 2009;144:245–52. 10.1016/j.pain.2009.03.024
    1. Tofthagen C, Donovan KA, Morgan MA et al. . Oxaliplatin-induced peripheral neuropathy's effects on health-related quality of life of colorectal cancer survivors. Support Care Cancer 2013;21:3307–13. 10.1007/s00520-013-1905-5
    1. Mols F, Beijers T, Lemmens V et al. . Chemotherapy-induced neuropathy and its association with quality of life among 2- to 11-year colorectal cancer survivors: results from the population-based PROFILES registry. J Clin Oncol 2013;31:2699–707. 10.1200/JCO.2013.49.1514
    1. Hershman DL, Lacchetti C, Dworkin RH et al. . Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 32:1941–67. 10.1200/JCO.2013.54.0914
    1. Ganz PA. Why and how to study the fate of cancer survivors: observations from the clinic and the research laboratory. Eur J Cancer 2003;39:2136–41. 10.1016/S0959-8049(03)00489-1
    1. Bell RF, Borzan J, Kalso E et al. . Food, pain, and drugs: does it matter what pain patients eat? Pain 2012;153:1993–6. 10.1016/j.pain.2012.05.018
    1. Rivat C, Richebé P, Laboureyras E et al. . Polyamine deficient diet to relieve pain hypersensitivity. Pain 2008;137:125–37. 10.1016/j.pain.2007.08.021
    1. Milovic V. Polyamines in the gut lumen: bioavailability and biodistribution. Eur J Gastroenterol Hepatol 2001;13:1021–5. 10.1097/00042737-200109000-00004
    1. Ji R-R, Kohno T, Moore KA et al. . Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci 2003;26:696–705. 10.1016/j.tins.2003.09.017
    1. Ferrier J, Bayet-Robert M, Pereira B et al. . A polyamine-deficient diet prevents oxaliplatin-induced acute cold and mechanical hypersensitivity in rats. PloS ONE 2013;8:e77828 10.1371/journal.pone.0077828
    1. Ramani D, De Bandt JP, Cynober L. Aliphatic polyamines in physiology and diseases. Clin Nutr 2014;33:14–22. 10.1016/j.clnu.2013.09.019
    1. Cipolla B, Guillí F, Moulinoux J-P. Polyamine-reduced diet in metastatic hormone-refractory prostate cancer (HRPC) patients. Biochem Soc Trans 2003;31:384–7. 10.1042/BST0310384
    1. Cipolla BG, Havouis R, Moulinoux JP. Polyamine contents in current foods: a basis for polyamine reduced diet and a study of its long term observance and tolerance in prostate carcinoma patients. Amino Acids 2007;33:203–12. 10.1007/s00726-007-0524-1
    1. Cipolla BG, Havouis R, Moulinoux J-P. Polyamine reduced diet (PRD) nutrition therapy in hormone refractory prostate cancer patients. Biomed Pharmacother 2010;64:363–8. 10.1016/j.biopha.2009.09.022
    1. Bouhassira D, Attal N, Alchaar H et al. . Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005;114:29–36. 10.1016/j.pain.2004.12.010
    1. Bouhassira D, Attal N, Fermanian J et al. . Development and validation of the Neuropathic Pain Symptom Inventory. Pain 2004;108:248–57. 10.1016/j.pain.2003.12.024
    1. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361–70. 10.1111/j.1600-0447.1983.tb09716.x
    1. Moulinoux JP, Quemener V, Khan NA. Biological significance of circulating polyamines in oncology. Cell Mol Biol 1991;37:773–83.
    1. Linsalata M, Russo F. Nutritional factors and polyamine metabolism in colorectal cancer. Nutrition 2008;24:382–9.
    1. Vickers AJ, Altman DG. Statistics notes: analysing controlled trials with baseline and follow up measurements. BMJ 2001;323:1123–4. 10.1136/bmj.323.7321.1123
    1. Verbeke G. Linear mixed models for longitudinal data. New York: Springer, 2009.
    1. Harris PA, Taylor R, Thielke R et al. . Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377–81. 10.1016/j.jbi.2008.08.010
    1. Park SB, Lin CSY, Krishnan AV et al. . Long-term neuropathy after oxaliplatin treatment: challenging the dictum of reversibility. Oncologist 2011;16:708–16. 10.1634/theoncologist.2010-0248
    1. André T, Boni C, Navarro M et al. . Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 2009;27:3109–16. 10.1200/JCO.2008.20.6771
    1. Pike CT, Birnbaum HG, Muehlenbein CE et al. . Healthcare costs and workloss burden of patients with chemotherapy-associated peripheral neuropathy in breast, ovarian, head and neck, and nonsmall cell lung cancer. Chemother Res Pr 2012;2012:913848.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren