Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 9/2018

01-09-2018 | Original Article – Clinical Oncology

Rechallenge with oxaliplatin and peripheral neuropathy in colorectal cancer patients

Authors: Sarah Besora, Cristina Santos, Cristina Izquierdo, Maria Mercedes Martinez-Villacampa, Jordi Bruna, Roser Velasco

Published in: Journal of Cancer Research and Clinical Oncology | Issue 9/2018

Login to get access

Abstract

Background

Oxaliplatin (OXA) is a cornerstone in the treatment of colorectal cancer (CRC). Retreatment with OXA is frequently considered as salvage treatment. OXA-induced neuropathy (OIN) is the most frequent and feared long-term side effect.

Patients and methods

CRC patients receiving at least twice OXA-based chemotherapy lines at our institution between June 2000 and July 2016 were reviewed. The aim of this study was to investigate whether retreatment with OXA increases the risk of developing new or worsening previous neuropathy. OIN was assessed by National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI), Total Neuropathy Score© (TNS) and nerve-conduction studies.

Results

106 patients were included in the analysis. Median age at OXA-based retreatment was 61.5 (20–83) years. After the first OXA-based chemotherapy treatment, 63.4% of patients developed OIN, 30.7 and 8.9% grades 2 and 3, respectively, after a median of 11 (1–17) cycles. After 30 (11–90) months of median to retreatment with a median of 8 (1–14) OXA cycles, 39.6, 22.6, and 0% of patients developed grade 1, 2, and 3 OIN, respectively. Worsening of the previous OIN was observed in one-third (31.1%) of all patients. OXA-cumulative dose was independently associated with greater risk of worsening OIN (p < 0.001). Non-significant trend towards higher TNSc© scores after retreatment was observed [5 (0–11) vs 6 (3–13), p = 0.083].

Conclusion

Retreatment with OXA in CRC patients is a feasible option even in patients who previously developed moderate or severe OIN. One-third of patients’ OIN was worsened by retreatment. Neurological monitoring should be considered.
Literature
go back to reference André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A. Investigators (2004) Multicenter international study of oxaliplatin/5-fluorouracil/leucovorin in the adjuvant treatment of colon cancer (MOSAIC). Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350(23):2343–2351. https://doi.org/10.1056/NEJMoa032709 CrossRefPubMed André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A. Investigators (2004) Multicenter international study of oxaliplatin/5-fluorouracil/leucovorin in the adjuvant treatment of colon cancer (MOSAIC). Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350(23):2343–2351. https://​doi.​org/​10.​1056/​NEJMoa032709 CrossRefPubMed
go back to reference André T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F, de Gramont A (2009) Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Onco 27(19):3109–3116. https://doi.org/10.1200/JCO.2008.20.6771 CrossRef André T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F, de Gramont A (2009) Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Onco 27(19):3109–3116. https://​doi.​org/​10.​1200/​JCO.​2008.​20.​6771 CrossRef
go back to reference Briani C, Argyriou AA, Izquierdo C, Velasco R, Campagnolo M, Alberti P, Frigeni B, Cacciavillani M, Bergamo F, Cortinovis D, Cazzaniga M, Bruna J et al (2014) Long-term course of oxaliplatin-induced polyneuropathy: a prospective 2-year follow-up study. J Peripher Nerv Syst 19(4):299–306. https://doi.org/10.1111/jns.12097 CrossRefPubMed Briani C, Argyriou AA, Izquierdo C, Velasco R, Campagnolo M, Alberti P, Frigeni B, Cacciavillani M, Bergamo F, Cortinovis D, Cazzaniga M, Bruna J et al (2014) Long-term course of oxaliplatin-induced polyneuropathy: a prospective 2-year follow-up study. J Peripher Nerv Syst 19(4):299–306. https://​doi.​org/​10.​1111/​jns.​12097 CrossRefPubMed
go back to reference Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F et al (2008) Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/ folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol 26(12):2006–2012. https://doi.org/10.1200/JCO.2007.14.9898 CrossRefPubMed Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F et al (2008) Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/ folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol 26(12):2006–2012. https://​doi.​org/​10.​1200/​JCO.​2007.​14.​9898 CrossRefPubMed
go back to reference Cavaletti G, Frigeni B, Lanzani F, Piatti M, Rota S, Briani C, Zara G, Plasmati R, Pastorelli F, Caraceni A, Pace A, Manicone M et al (2007) The Total Neuropathy Score as an assessment tool for grading the course of chemotherapy-induced peripheral neurotoxicity: comparison with the National Cancer Institute-Common Toxicity Scale. J Peripher Nerv Syst 12(3):210–215. https://doi.org/10.1111/j.1529-8027.2007.00141.x CrossRefPubMed Cavaletti G, Frigeni B, Lanzani F, Piatti M, Rota S, Briani C, Zara G, Plasmati R, Pastorelli F, Caraceni A, Pace A, Manicone M et al (2007) The Total Neuropathy Score as an assessment tool for grading the course of chemotherapy-induced peripheral neurotoxicity: comparison with the National Cancer Institute-Common Toxicity Scale. J Peripher Nerv Syst 12(3):210–215. https://​doi.​org/​10.​1111/​j.​1529-8027.​2007.​00141.​x CrossRefPubMed
go back to reference Cavaletti G, Cornblath DR, Merkies IS, Postma TJ, Rossi E, Frigeni B, Alberti P, Bruna J, Velasco R, Argyriou AA, Kalofonos HP, Psimaras D et al (2013) The chemotherapy induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings. Ann Oncol 24(2):454–462. https://doi.org/10.1093/annonc/mds329 CrossRefPubMed Cavaletti G, Cornblath DR, Merkies IS, Postma TJ, Rossi E, Frigeni B, Alberti P, Bruna J, Velasco R, Argyriou AA, Kalofonos HP, Psimaras D et al (2013) The chemotherapy induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings. Ann Oncol 24(2):454–462. https://​doi.​org/​10.​1093/​annonc/​mds329 CrossRefPubMed
go back to reference Cornblath DR, Chaudhry V, Carter K, Lee D, Seysedadr M, Miernicki M, Joh T (1999) Total neuropathy score: validation and reliability study. Neurology 53:1660–1664CrossRefPubMed Cornblath DR, Chaudhry V, Carter K, Lee D, Seysedadr M, Miernicki M, Joh T (1999) Total neuropathy score: validation and reliability study. Neurology 53:1660–1664CrossRefPubMed
go back to reference de Gramont A, Louvet C, Andre´ T et al (2002) Infusional 5-fluorouracil: Bimonthly leucovorin–5-fluorouracil with oxaliplatin or irinotecan: the FOLFOX and FOLFIRI regimens. In: Bleiberg H, Kemeny N, Rougier P, Wilke H (eds) Colorectal cancer: a clinical guide to therapy. Martin Dunitz, London, pp 563–569. https://doi.org/10.1093/annonc/mdf278 CrossRef de Gramont A, Louvet C, Andre´ T et al (2002) Infusional 5-fluorouracil: Bimonthly leucovorin–5-fluorouracil with oxaliplatin or irinotecan: the FOLFOX and FOLFIRI regimens. In: Bleiberg H, Kemeny N, Rougier P, Wilke H (eds) Colorectal cancer: a clinical guide to therapy. Martin Dunitz, London, pp 563–569. https://​doi.​org/​10.​1093/​annonc/​mdf278 CrossRef
go back to reference de Gramont A, Chibaudel B, Bourges O, Perez-Staub N, Tournigand C, Maindrault-Goebel F, André T, Larsen AK, Afchain P, Louvet C (2009) Definition of oxaliplatin sensitivity in patients with advanced colorectal cancer previously treated with oxaliplatin-based therapy. J Clin Oncol 27(15 Suppl):4024 (Abstr) de Gramont A, Chibaudel B, Bourges O, Perez-Staub N, Tournigand C, Maindrault-Goebel F, André T, Larsen AK, Afchain P, Louvet C (2009) Definition of oxaliplatin sensitivity in patients with advanced colorectal cancer previously treated with oxaliplatin-based therapy. J Clin Oncol 27(15 Suppl):4024 (Abstr)
go back to reference 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 (2003) 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 21:2059–2069. https://doi.org/10.1200/JCO.2003.11.126 CrossRefPubMed 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 (2003) 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 21:2059–2069. https://​doi.​org/​10.​1200/​JCO.​2003.​11.​126 CrossRefPubMed
go back to reference Tournigand C, Cervantes A, Figer A, Lledo G, Flesch M, Buyse M, Mineur L, Carola E, Etienne PL, Rivera F, Chirivella I, Perez-Staub N et al (2006) OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-go fashion in advanced colorectal cancer—a GERCOR study. J Clin Oncol 24:394–400. https://doi.org/10.1200/JCO.2005.03.0106 CrossRefPubMed Tournigand C, Cervantes A, Figer A, Lledo G, Flesch M, Buyse M, Mineur L, Carola E, Etienne PL, Rivera F, Chirivella I, Perez-Staub N et al (2006) OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-go fashion in advanced colorectal cancer—a GERCOR study. J Clin Oncol 24:394–400. https://​doi.​org/​10.​1200/​JCO.​2005.​03.​0106 CrossRefPubMed
go back to reference Velasco R, Bruna J (2010) Chemotherapy-induced peripheral neuropathy: an unresolved issue. Neurologia 25(2):116–131 (PMID: 20487712).CrossRefPubMed Velasco R, Bruna J (2010) Chemotherapy-induced peripheral neuropathy: an unresolved issue. Neurologia 25(2):116–131 (PMID: 20487712).CrossRefPubMed
go back to reference Velasco R, Bruna J, Briani C, Argyriou AA, Cavaletti G, Alberti P, Frigeni B, Cacciavillani M, Lonardi S, Cortinovis D, Cazzaniga M, Santos C et al (2014) Early predictors of oxaliplatin induced cumulative neuropathy in colorectal cancer patients. J Neurol Neurosurg Psychiatry 85(4):392–398. https://doi.org/10.1136/jnnp-2013-305334 CrossRefPubMed Velasco R, Bruna J, Briani C, Argyriou AA, Cavaletti G, Alberti P, Frigeni B, Cacciavillani M, Lonardi S, Cortinovis D, Cazzaniga M, Santos C et al (2014) Early predictors of oxaliplatin induced cumulative neuropathy in colorectal cancer patients. J Neurol Neurosurg Psychiatry 85(4):392–398. https://​doi.​org/​10.​1136/​jnnp-2013-305334 CrossRefPubMed
Metadata
Title
Rechallenge with oxaliplatin and peripheral neuropathy in colorectal cancer patients
Authors
Sarah Besora
Cristina Santos
Cristina Izquierdo
Maria Mercedes Martinez-Villacampa
Jordi Bruna
Roser Velasco
Publication date
01-09-2018
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 9/2018
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-018-2691-8

Other articles of this Issue 9/2018

Journal of Cancer Research and Clinical Oncology 9/2018 Go to the issue