Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

The incidence of acute oxaliplatin-induced neuropathy and its impact on treatment in the first cycle: a systematic review

Authors: Endale Gebreegziabher Gebremedhn, Peter John Shortland, David Anthony Mahns

Published in: BMC Cancer | Issue 1/2018

Login to get access

Abstract

Background

Although acute oxaliplatin-induced neuropathy (OXIPN) is frequently regarded to be transient, recent studies have reported prolongation of infusion times, dose reduction and treatment cessation following the first dose of oxaliplatin in quarter of patients. Acute OXIPN is also a well-established risk factor for chronic neuropathy. However, there is underreporting of these parameters during the acute phase (≤ 14 days). This paper systematically reviews the incidence of acute OXIPN and its impact on treatment in the first cycle.

Methods

A systematic literature search was performed using PubMed and Medline. Published original articles were included if they described details about prevalence of oxaliplatin-induced acute neuropathy.

Results

Fourteen studies, comprised of 6211 patients were evaluated. The majority of patients were treated with oxaliplatin in combination with leucovorin and fluorouracil (FOLFOX). Most studies used the National Cancer Institute Common Toxicity Criteria to assess acute neuropathy. Acute neuropathy (Grades 1–4) was the most common event with prevalence ranging from 4–98%, followed by haematological (1.4–81%) and gastrointestinal (1.2–67%) toxicities, respectively. Drug regimens, starting dose of oxaliplatin and neuropathy assessment tools varied across studies. In addition, moderate to severe toxicities were common in patients that received a large dose of oxaliplatin (> 85 mg/m2) and/ or combined drugs. The majority of studies did not report the factors affecting acute neuropathy namely the range (minimal) doses required to evoke acute neuropathy, patient and clinical risk factors. In addition, there was no systematic reporting of the number of patients subjected to prolonged infusion, dose reduction, treatment delay and treatment cessation during the acute phase.

Conclusion

Despite the heterogeneity of studies regarding oxaliplatin starting dose, drug regimen, neuropathy assessment tools and study design, a large number of patients developed acute neuropathy. To develop a better preventive and therapeutic guideline for acute/chronic neuropathy, a prospective study should be conducted in a large cohort of patients in relation to drug regimen, starting/ranges (minimal) of doses producing acute neuropathy, treatment compliance, patient and clinical risk factors using a standardised neuropathy assessment tool.
Literature
1.
Parkin DMBF, Ferlay J, Pisani P. Global Cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.CrossRefPubMed
2.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMed
3.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86.CrossRefPubMed
4.
Gill S, Loprinzi CL, Sargent DJ, Thome SD, Alberts SR, Haller DG, Benedetti J, Francini G, Shepherd LE, Francois Seitz J, Labianca R, Chen W, Cha SS, Heldebrant MP, Goldberg RM. Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much? J Clin Oncol. 2004;22(10):1797–806.CrossRefPubMed
5.
Ragnhammar PHL. A systematic overview of chemotherapy effects in colorectal cancer. Acta Oncol. 2009;40(2–3):282–308.
6.
Kalofonos HP, Aravantinos G, Kosmidis P, Papakostas P, Economopoulos T, Dimopoulos M, Skarlos D, Bamias A, Pectasides D, Chalkidou S, Karina M, Koutras A, Samantas E, Bacoyiannis C, Samelis GF, Basdanis G, Kalfarentzos F, Fountzilas G. Irinotecan or oxaliplatin combined with leucovorin and 5-fluorouracil as first-line treatment in advanced colorectal cancer: a multicenter, randomized, phase II study. Ann Oncol. 2005;16(6):869–77.CrossRefPubMed
7.
André TBC, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350:2343–51.CrossRefPubMed
8.
Rothenberg ML, Oza AM, Bigelow RH, Berlin JD, Marshall JL, Ramanathan RK, Hart LL, Gupta S, Garay CA, Burger BG, Le Bail N, Haller DG. Superiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil-leucovorin: interim results of a phase III trial. J Clin Oncol. 2003;21(11):2059–69.CrossRefPubMed
9.
Machover DD-RE, De Gramont A, Schilf A, Gastiaburu JJ, Brienza S, Itzhaki M, Metzger G, N'Daw D, Vignoud J, Abad A, Francois E, Gamelin E, Marty M, Sastre J, Seitz JE, Ychou M. Two consecutive phase II studies of oxaliplatin (L-OHP) for treatment of patients with advanced colorectal carcinoma who were resistant to previous treatment with fluoropyrimidines. Ann Oncol. 1996;7:95–8.CrossRefPubMed
10.
Becouarn YYM, Ducreux M, Borel C, Bertheault-Cvitkovic F, Seitz JF, Nasca S, Nguyen TD, Paillot B, Raoul JL, Duffour J, Fandi A, Dupont-Andr G, Rougier P. Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. J Clin Oncol. 1998;16(8):2739–44.CrossRefPubMed
11.
Diaz-Rubio ESJ, Zaniboni A, Labianca R, Cortes-Funes H, De Braud F, Boni C, Benavides M, Dallavalle G, Homerin M. Oxaliplatin as single agent in previously untreated colorectal carcinoma patients: a phase II multicentric study. Ann Oncol. 1998;9:105–8.CrossRefPubMed
12.
Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Pitot HC, Alberts SR. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2004;22(1):23–30.CrossRefPubMed
13.
Giacchetti SPB, Zidani R, Le Bail N, Faggiuolo R, Focan C, Chollet P, Llory JF, Letourneau Y, Coudert B, Bertheaut-Cvitkovic F, Larregain-Fournier D, Rol AL, Walter S, Adam R, Misset JL, Le’vi F. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil–leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2000;18:136–47.CrossRefPubMed
14.
Andre TBK, Bouche O’, Bensmaine MA, Louvet C, Franc E’, Lucas V, Desseigne F, Beerblock K, Bouche O’, Carola E, Merrouche Y, Morvan F, Dupont-Andre G, de Gramont A. Multicenter phase II study of bimonthly high-dose leucovorin, fluorouracil infusion, and oxaliplatin for metastatic colorectal cancer resistant to the same leucovorin and fluorouracil regimen. JC Oncol. 1999;17:3560–8.CrossRef
15.
Livi FMJ, Brienza S, Adam R, Metzger G, Itzakhi M, Caussanel JP, Kunstlinger F, Lecouturier S, Descorps-Decle're A, Jasmin C, Bismuth H, Reinberg A. A Chronopharmacologic phase II clinical trial with 5-fluorouracil, folinic acid, and oxaliplatin using an ambulatory multichannel programmable pump. Cancer Chemother Pharmacol. 1992;69(4):893–900.
16.
Xu N, Fang WJ, Zhang XC, Yu LF, Bao HY, Shi GM, Huang S, Shen P. A phase II trial of oxaliplatin, folinic acid, and 5-fluorouracil (FOLFOX4) as first-line chemotherapy in advanced colorectal cancer: a China single-center experience. Cancer Investig. 2007;25(7):599–605.CrossRef
17.
Argyriou AA, Cavaletti G, Briani C, Velasco R, Bruna J, Campagnolo M, Alberti P, Bergamo F, Cortinovis D, Cazzaniga M, Santos C, Papadimitriou K, Kalofonos HP. Clinical pattern and associations of oxaliplatin acute neurotoxicity: a prospective study in 170 patients with colorectal cancer. Cancer. 2013;119(2):438–44.CrossRefPubMed
18.
Park SB, Goldstein D, Lin CS, Krishnan AV, Friedlander ML, Kiernan MC. Acute abnormalities of sensory nerve function associated with oxaliplatin-induced neurotoxicity. J Clin Oncol. 2009;27(8):1243–9.CrossRefPubMed
19.
Alejandro LM, Behrendt CE, Chen K, Openshaw H, Shibata S. Predicting acute and persistent neuropathy associated with oxaliplatin. Am J Clin Oncol. 2013;36(4):331–7.CrossRefPubMedCentralPubMed
20.
Velasco R, Bruna J, Briani C, Argyriou AA, Cavaletti G, Alberti P, Frigeni B, Cacciavillani M, Lonardi S, Cortinovis D, Cazzaniga M, Santos C, Kalofonos HP. Early predictors of oxaliplatin-induced cumulative neuropathy in colorectal cancer patients. J Neurol Neurosurg Psychiatry. 2014;85(4):392–8.CrossRefPubMed
21.
Attal N, Bouhassira D, Gautron M, Vaillant JN, Mitry E, Lepere C, Rougier P, Guirimand F. Thermal hyperalgesia as a marker of oxaliplatin neurotoxicity: a prospective quantified sensory assessment study. Pain. 2009;144(3):245–52.CrossRefPubMed
22.
Saadati HSMW. Oxaliplatin-induced hyperexcitability syndrome in a patient with pancreatic cancer. J Pancreas. 2009;10(4):459–61.
23.
Argyriou AA, Polychronopoulos P, Iconomou G, Chroni E, Kalofonos HP. A review on oxaliplatin-induced peripheral nerve damage. Cancer Treat Rev. 2008;34(4):368–77.CrossRefPubMed
24.
Grothey A, Goldberg RM. A review of oxaliplatin and its clinical use in colorectal cancer. Expert Opin Pharmacother. 2004;5(10):2159–70.CrossRefPubMed
25.
Storey DJ, Sakala M, McLean CM, Phillips HA, Dawson LK, Wall LR, Fallon MT, Clive S. Capecitabine combined with oxaliplatin (CapOx) in clinical practice: how significant is peripheral neuropathy? Ann Oncol. 2010;21(8):1657–61.CrossRefPubMed
26.
Gamelin L, Capitain O, Morel A, Dumont A, Traore S, Anne le B, Gilles S, Boisdron-Celle M, Gamelin E. Predictive factors of oxaliplatin neurotoxicity: the involvement of the oxalate outcome pathway. Clin Cancer Res 2007; 13 (21):6359–6368.
27.
28.
Loupakis F, Stein A, Ychou M, Hermann F, Salud A, Osterlund P. A review of clinical studies and practical guide for the administration of triplet chemotherapy regimens with bevacizumab in first-line metastatic colorectal cancer. Target Oncol. 2016;11(3):293–308.CrossRefPubMed
29.
Pfeiffer P, Sorbye H, Ehrsson H, Fokstuen T, Mortensen JP, Baltesgard L, Tveit KM, Ogreid D, Starkhammar H, Wallin I, Qvortrup C, Glimelius B. Short-time infusion of oxaliplatin in combination with capecitabine (XELOX30) as second-line therapy in patients with advanced colorectal cancer after failure to irinotecan and 5-fluorouracil. Ann Oncoly. 2006;17(2):252–8.CrossRef
30.
Pfeiffer P, Hahn P, Anita JH. Short-time infusion of oxaliplatin (eloxatin®) in combination with capecitabine (xeloda®) in patients with advanced colorectal cancer. Acta Oncol. 2009;42(8):832–6.CrossRef
31.
Yanai T, Hashimoto H, Kato K, Hamaguchi T, Yamada Y, Shimada Y, Yamamoto H. Successful rechallenge for oxaliplatin hypersensitivity reactions in patients with metastatic colorectal cancer. Anticancer Res. 2012;32:5521–6.
32.
Argyriou AA, Velasco R, Briani C, Cavaletti G, Bruna J, Alberti P, Cacciavillani M, Lonardi S, Santos C, Cortinovis D, Cazzaniga M, Kalofonos HP. Peripheral neurotoxicity of oxaliplatin in combination with 5-fluorouracil (FOLFOX) or capecitabine (XELOX): a prospective evaluation of 150 colorectal cancer patients. Ann Oncol. 2012;23(12):3116–22.
33.
Ravaioli A, Marangolo M, Pasquini E, Rossi A, Amadori D, Cruciani G, Tassinari D, Oliverio G, Giovanis P, Turci D, Zumaglini F, Nicolini M, Panzini I. Bolus fluorouracil and leucovorin with oxaliplatin as first-line treatment in metastatic colorectal cancer. J Clin Oncol. 2002;20(10):2545–50.CrossRefPubMed
34.
Shields AF, Zalupski MM, Marshall JL, Meropol NJ. Treatment of advanced colorectal carcinoma with oxaliplatin and capecitabine: a phase II trial. Cancer. 2004;100(3):531–7.CrossRefPubMed
35.
Sorbye H, Glimelius B, Berglund A, Fokstuen T, Tveit KM, Braendengen M, Ogreid D, Dahl O. Multicenter phase II study of Nordic fluorouracil and folinic acid bolus schedule combined with oxaliplatin as first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2004;22(1):31–8.CrossRefPubMed
36.
Land SR, Kopec JA, Cecchini RS, Ganz PA, Wieand HS, Colangelo LH, Murphy K, Kuebler JP, Seay TE, Needles BM, Bearden JD 3rd, Colman LK, Lanier KS, Pajon ER Jr, Cella D, Smith RE, O'Connell MJ, Costantino JP, Wolmark N. Neurotoxicity from oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: NSABP C-07. J Clin Oncol. 2007;25(16):2205–11.CrossRefPubMed
37.
Schmoll HJ, Cartwright T, Tabernero J, Nowacki MP, Figer A, Maroun J, Price T, Lim R, Van Cutsem E, Park YS, McKendrick J, Topham C, Soler-Gonzalez G, de Braud F, Hill M, Sirzen F, Haller DG. Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. J Clin Oncol. 2007;25(1):102–9.CrossRefPubMed
38.
Davidov DN. Oxaliplatin/5-fluorouracil/leucovorin in the treatment of patients with metastatic colorectal cancer. Journal of IMAB - Annual Proceeding (Scientific Papers). 2013;19(3):476–80.CrossRef
39.
Beijers AJ, Mols F, Vreugdenhil G. A systematic review on chronic oxaliplatin-induced peripheral neuropathy and the relation with oxaliplatin administration. Support Care Cancer. 2014;22(7):1999–2007.CrossRefPubMed
40.
Pachman DRQR, Seisler DK, Smith EM, Beutler AS, Ta LE, Lafky JM, Wagner-Johnston ND, Ruddy KJ, Dakhil S, Staff NP, Grothey A, Loprinzi CL. Clinical course of oxaliplatin-induced neuropathy: results from the randomized phase III trial N08CB (alliance). J Clin Oncol. 2015;33(30):3416–22.CrossRefPubMedCentralPubMed
41.
Grothey A. Clinical management of oxaliplatin-associated neurotoxicity. Clin Colorectal Cancer. 2005;5:S38–46.CrossRefPubMed
42.
Pulvers JN, Marx G. Factors associated with the development and severity of oxaliplatin-induced peripheral neuropathy: a systematic review. Asia Pac J Clin Oncol. 2017;13(6):345–55.
43.
Drott JE, Starkhammar H, Börjeson S, Berterö CM. OxaliplatiniInduced neurotoxicity among patients with colorectal cancer-documentation. Open J Nurs. 2014;4:265–74.CrossRef
44.
Vatandoust S, Joshi R, Pittman KB, Esterman A, Broadbridge V, Adams J, Singhal N, Yeend S, Price TJ. A descriptive study of persistent oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer. Support Care Cancer. 2014;22(2):513–8.CrossRefPubMed
45.
Postma TJHJ, Muller MJ, Ossenkoppele GJ, Vermorken JB, Aaronson NK. Pitfalls in grading severity of chemotherapy-induced peripheral neuropathy. Annuls of Oncology. 1998;9:739–44.CrossRef
46.
Park SB, Lin CS, Kiernan MC. Nerve excitability assessment in chemotherapy-induced neurotoxicity. J Vis Exp. 2012;62:e3439.
47.
Adelsbergera HQS, Grosskreutz J, Lepier A, Eckel F, Lersch C. The chemotherapeutic oxaliplatin alters voltage-gated Naq+ channel kinetics on rat sensory neurons. Eur J Pharmacol. 2000;406:25–32.CrossRef
48.
Webster RG, Brain KL, Wilson RH, Grem JL, Vincent A. Oxaliplatin induces hyperexcitability at motor and autonomic neuromuscular junctions through effects on voltage-gated sodium channels. Br J Pharmacol. 2005;146(7):1027–39.CrossRefPubMedCentralPubMed
49.
Bouhours M, Sternberg D, Davoine CS, Ferrer X, Willer JC, Fontaine B, Tabti N. Functional characterization and cold sensitivity of T1313A, a new mutation of the skeletal muscle sodium channel causing paramyotonia congenita in humans. J Physiol. 2004;554(Pt 3):635–47.CrossRefPubMed
50.
SB Rutkove SB. Effects of temperature on neuromuscular electrophysiology. Muscle Nerve. 2001;24:867–82.CrossRef
51.
Park SB, Lin CS, Krishnan AV, Goldstein D, Friedlander ML, Kiernan MC. Oxaliplatin-induced neurotoxicity: changes in axonal excitability precede development of neuropathy. Brain. 2009;132(Pt 10):2712–23.CrossRefPubMed
Metadata
Title
The incidence of acute oxaliplatin-induced neuropathy and its impact on treatment in the first cycle: a systematic review
Authors
Endale Gebreegziabher Gebremedhn
Peter John Shortland
David Anthony Mahns
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4185-0

Other articles of this Issue 1/2018

BMC Cancer 1/2018 Go to the issue

Case report

Combination of anti-PD-1 therapy and stereotactic radiosurgery for a gastric cancer patient with brain metastasis: a case report

Research article

Curcumin inhibits proliferation, migration, invasion and promotes apoptosis of retinoblastoma cell lines through modulation of miR-99a and JAK/STAT pathway

Research article

AZGP1 inhibits soft tissue sarcoma cells invasion and migration

Research article

A novel combined systemic inflammation-based score can predict survival of intermediate-to-advanced hepatocellular carcinoma patients undergoing transarterial chemoembolization

Research article

Treatment selection of early stage non-small cell lung cancer: the role of the patient in clinical decision making

Research article

Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits