Skip to main content
Top
Published in: Supportive Care in Cancer 12/2016

01-12-2016 | Original Article

Comparison of oxaliplatin and paclitaxel-induced neuropathy (Alliance A151505)

Authors: Deirdre R. Pachman, Rui Qin, Drew Seisler, Ellen M. Lavoie Smith, Suneetha Kaggal, Paul Novotny, Kathryn J. Ruddy, Jacqueline M. Lafky, Lauren E. Ta, Andreas S. Beutler, Nina D. Wagner-Johnston, Nathan P. Staff, Axel Grothey, Patrick M. Dougherty, Guido Cavaletti, Charles L. Loprinzi

Published in: Supportive Care in Cancer | Issue 12/2016

Login to get access

Abstract

Purpose

Oxaliplatin and paclitaxel are commonly used chemotherapies associated with acute and chronic neuropathies. There is a need to better understand the similarities and differences of these clinical syndromes.

Methods

Neuropathy data were pooled from patients receiving adjuvant oxaliplatin and weekly paclitaxel or every 3 weeks of paclitaxel. Patients completed daily questionnaires after each chemotherapy dose and the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for patients with chemotherapy-induced peripheral neuropathy before each chemotherapy cycle and for 12 months post-treatment.

Results

Acute neuropathy symptoms from both drugs peaked around day 3. Acute symptoms experienced in cycle 1 predicted occurrence in subsequent cycles. Paclitaxel-induced acute symptoms were similar in intensity in each cycle and largely resolved between cycles. Oxaliplatin-induced acute symptoms were about half as severe in the first cycle as in later cycles and did not resolve completely between cycles. Both drugs caused a predominantly sensory chronic neuropathy (with numbness and tingling being more common than pain). Oxaliplatin-induced neuropathy worsened after the completion of treatment and began to improve 3 months post-treatment. In contrast, paclitaxel-induced neuropathy began improving immediately after chemotherapy cessation. During treatment, the incidence of paclitaxel sensory symptoms was similar in the hands and feet; with oxaliplatin, the hands were affected more than the feet. Both paclitaxel- and oxaliplatin-induced acute neurotoxicity appeared to predict the severity of chronic neuropathy, more prominently with oxaliplatin.

Conclusions

Knowledge of the similarities and differences between neuropathy syndromes may provide insight into their underlying pathophysiology and inform future research to identify preventative treatment approaches.
Literature
1.
go back to reference Pachman DR, Qin R, Seisler DK, Smith EM, Beutler AS, Ta LE, Lafky JM, Wagner-Johnston ND, Ruddy KJ, Dakhil S, Staff NP, Grothey A, Loprinzi CL (2015) Clinical course of oxaliplatin-induced neuropathy: results from the randomized phase III trial N08CB (Alliance). J Clin Oncol Pachman DR, Qin R, Seisler DK, Smith EM, Beutler AS, Ta LE, Lafky JM, Wagner-Johnston ND, Ruddy KJ, Dakhil S, Staff NP, Grothey A, Loprinzi CL (2015) Clinical course of oxaliplatin-induced neuropathy: results from the randomized phase III trial N08CB (Alliance). J Clin Oncol
2.
go back to reference Loprinzi CL, Reeves BN, Dakhil SR, Sloan JA, Wolf SL, Burger KN, Kamal A, Le-Lindqwister NA, Soori GS, Jaslowski AJ, Novotny PJ, Lachance DH (2011) Natural history of paclitaxel-associated acute pain syndrome: prospective cohort study NCCTG N08C1. J Clin Oncol 29:1472–1478CrossRefPubMedPubMedCentral Loprinzi CL, Reeves BN, Dakhil SR, Sloan JA, Wolf SL, Burger KN, Kamal A, Le-Lindqwister NA, Soori GS, Jaslowski AJ, Novotny PJ, Lachance DH (2011) Natural history of paclitaxel-associated acute pain syndrome: prospective cohort study NCCTG N08C1. J Clin Oncol 29:1472–1478CrossRefPubMedPubMedCentral
3.
go back to reference Reeves BN, Dakhil SR, Sloan JA, Wolf SL, Burger KN, Kamal A, Le-Lindqwister NA, Soori GS, Jaslowski AJ, Kelaghan J, Novotny PJ, Lachance DH, Loprinzi CL (2012) Further data supporting that paclitaxel-associated acute pain syndrome is associated with development of peripheral neuropathy: North Central Cancer Treatment Group trial N08C1. Cancer 118:5171–5178CrossRefPubMedPubMedCentral Reeves BN, Dakhil SR, Sloan JA, Wolf SL, Burger KN, Kamal A, Le-Lindqwister NA, Soori GS, Jaslowski AJ, Kelaghan J, Novotny PJ, Lachance DH, Loprinzi CL (2012) Further data supporting that paclitaxel-associated acute pain syndrome is associated with development of peripheral neuropathy: North Central Cancer Treatment Group trial N08C1. Cancer 118:5171–5178CrossRefPubMedPubMedCentral
4.
go back to reference Lehky TJ, Leonard GD, Wilson RH, Grem JL, Floeter MK (2004) Oxaliplatin-induced neurotoxicity: acute hyperexcitability and chronic neuropathy. Muscle Nerve 29:387–392CrossRefPubMed Lehky TJ, Leonard GD, Wilson RH, Grem JL, Floeter MK (2004) Oxaliplatin-induced neurotoxicity: acute hyperexcitability and chronic neuropathy. Muscle Nerve 29:387–392CrossRefPubMed
5.
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, Cavaletti G, Kalofonos HP (2014) Long-term course of oxaliplatin-induced polyneuropathy: a prospective 2-year follow-up study. J Peripher Nerv Syst 19:299–306CrossRefPubMed Briani C, Argyriou AA, Izquierdo C, Velasco R, Campagnolo M, Alberti P, Frigeni B, Cacciavillani M, Bergamo F, Cortinovis D, Cazzaniga M, Bruna J, Cavaletti G, Kalofonos HP (2014) Long-term course of oxaliplatin-induced polyneuropathy: a prospective 2-year follow-up study. J Peripher Nerv Syst 19:299–306CrossRefPubMed
6.
go back to reference Kidwell KM, Yothers G, Ganz PA, Land SR, Ko CY, Cecchini RS, Kopec JA, Wolmark N (2012) Long-term neurotoxicity effects of oxaliplatin added to fluorouracil and leucovorin as adjuvant therapy for colon cancer: results from National Surgical Adjuvant Breast and Bowel Project trials C-07 and LTS-01. Cancer Kidwell KM, Yothers G, Ganz PA, Land SR, Ko CY, Cecchini RS, Kopec JA, Wolmark N (2012) Long-term neurotoxicity effects of oxaliplatin added to fluorouracil and leucovorin as adjuvant therapy for colon cancer: results from National Surgical Adjuvant Breast and Bowel Project trials C-07 and LTS-01. Cancer
7.
go back to reference Mols F, Beijers T, Lemmens V, van den Hurk CJ, Vreugdenhil G, van de Poll-Franse LV (2013) 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 31:2699–2707CrossRefPubMed Mols F, Beijers T, Lemmens V, van den Hurk CJ, Vreugdenhil G, van de Poll-Franse LV (2013) 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 31:2699–2707CrossRefPubMed
8.
go back to reference Pietrangeli A, Leandri M, Terzoli E, Jandolo B, Garufi C (2006) Persistence of high-dose oxaliplatin-induced neuropathy at long-term follow-up. Eur Neurol 56:13–16CrossRefPubMed Pietrangeli A, Leandri M, Terzoli E, Jandolo B, Garufi C (2006) Persistence of high-dose oxaliplatin-induced neuropathy at long-term follow-up. Eur Neurol 56:13–16CrossRefPubMed
9.
go back to reference Loprinzi CL, Maddocks-Christianson K, Wolf SL, Rao RD, Dyck PJ, Mantyh P (2007) The paclitaxel acute pain syndrome: sensitization of nociceptors as the putative mechanism. Cancer J 13:399–403CrossRefPubMed Loprinzi CL, Maddocks-Christianson K, Wolf SL, Rao RD, Dyck PJ, Mantyh P (2007) The paclitaxel acute pain syndrome: sensitization of nociceptors as the putative mechanism. Cancer J 13:399–403CrossRefPubMed
10.
go back to reference Loprinzi CL, Qin R, Dakhil SR, Fehrenbacher L, Flynn KA, Atherton P, Seisler D, Qamar R, Lewis GC, Grothey A (2014) Phase III randomized, placebo-controlled, double-blind study of intravenous calcium and magnesium to prevent oxaliplatin-induced sensory neurotoxicity (N08CB/Alliance). J Clin Oncol 32:997–1005CrossRefPubMed Loprinzi CL, Qin R, Dakhil SR, Fehrenbacher L, Flynn KA, Atherton P, Seisler D, Qamar R, Lewis GC, Grothey A (2014) Phase III randomized, placebo-controlled, double-blind study of intravenous calcium and magnesium to prevent oxaliplatin-induced sensory neurotoxicity (N08CB/Alliance). J Clin Oncol 32:997–1005CrossRefPubMed
11.
go back to reference de Boer AG, van Lanschot JJ, Stalmeier PF, van Sandick JW, Hulscher JB, de Haes JC, Sprangers MA (2004) Is a single-item visual analogue scale as valid, reliable and responsive as multi-item scales in measuring quality of life? Qual Life Res 13:311–320CrossRefPubMed de Boer AG, van Lanschot JJ, Stalmeier PF, van Sandick JW, Hulscher JB, de Haes JC, Sprangers MA (2004) Is a single-item visual analogue scale as valid, reliable and responsive as multi-item scales in measuring quality of life? Qual Life Res 13:311–320CrossRefPubMed
12.
go back to reference Hauser K, Walsh D (2008) Visual analogue scales and assessment of quality of life in cancer. J Support Oncol 6:277–282PubMed Hauser K, Walsh D (2008) Visual analogue scales and assessment of quality of life in cancer. J Support Oncol 6:277–282PubMed
13.
go back to reference Kindler CH, Harms C, Amsler F, Ihde-Scholl T, Scheidegger D (2000) The visual analog scale allows effective measurement of preoperative anxiety and detection of patients’ anesthetic concerns. Anesth Analg 90:706–712CrossRefPubMed Kindler CH, Harms C, Amsler F, Ihde-Scholl T, Scheidegger D (2000) The visual analog scale allows effective measurement of preoperative anxiety and detection of patients’ anesthetic concerns. Anesth Analg 90:706–712CrossRefPubMed
14.
go back to reference Lavoie Smith EM, Barton DL, Qin R, Steen PD, Aaronson NK, Loprinzi CL (2013) Assessing patient-reported peripheral neuropathy: the reliability and validity of the European Organization for Research and Treatment of Cancer QLQ-CIPN20 Questionnaire. Qual Life Res 22:2787–2799CrossRefPubMedPubMedCentral Lavoie Smith EM, Barton DL, Qin R, Steen PD, Aaronson NK, Loprinzi CL (2013) Assessing patient-reported peripheral neuropathy: the reliability and validity of the European Organization for Research and Treatment of Cancer QLQ-CIPN20 Questionnaire. Qual Life Res 22:2787–2799CrossRefPubMedPubMedCentral
15.
go back to reference Cavaletti G, Cornblath DR, Merkies IS, Postma TJ, Rossi E, Frigeni B, et al. (2013) The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings. Ann Oncol 24:454–462CrossRefPubMed Cavaletti G, Cornblath DR, Merkies IS, Postma TJ, Rossi E, Frigeni B, et al. (2013) The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings. Ann Oncol 24:454–462CrossRefPubMed
16.
go back to reference Alberti P, Rossi E, Cornblath DR, Merkies IS, Postma TJ, Frigeni B, et al. (2014) Physician-assessed and patient-reported outcome measures in chemotherapy-induced sensory peripheral neurotoxicity: two sides of the same coin. Ann Oncol 25:257–264CrossRefPubMed Alberti P, Rossi E, Cornblath DR, Merkies IS, Postma TJ, Frigeni B, et al. (2014) Physician-assessed and patient-reported outcome measures in chemotherapy-induced sensory peripheral neurotoxicity: two sides of the same coin. Ann Oncol 25:257–264CrossRefPubMed
17.
go back to reference Adelsberger H, Quasthoff S, Grosskreutz J, Lepier A, Eckel F, Lersch C (2000) The chemotherapeutic oxaliplatin alters voltage-gated Na(+) channel kinetics on rat sensory neurons. Eur J Pharmacol 406:25–32CrossRefPubMed Adelsberger H, Quasthoff S, Grosskreutz J, Lepier A, Eckel F, Lersch C (2000) The chemotherapeutic oxaliplatin alters voltage-gated Na(+) channel kinetics on rat sensory neurons. Eur J Pharmacol 406:25–32CrossRefPubMed
18.
go back to reference Park SB, Lin CS, Krishnan AV, Goldstein D, Friedlander ML, Kiernan MC (2011) Dose effects of oxaliplatin on persistent and transient Na+ conductances and the development of neurotoxicity. PLoS One 6:e18469CrossRefPubMedPubMedCentral Park SB, Lin CS, Krishnan AV, Goldstein D, Friedlander ML, Kiernan MC (2011) Dose effects of oxaliplatin on persistent and transient Na+ conductances and the development of neurotoxicity. PLoS One 6:e18469CrossRefPubMedPubMedCentral
19.
go back to reference Sakurai M, Egashira N, Kawashiri T, Yano T, Ikesue H, Oishi R (2009) Oxaliplatin-induced neuropathy in the rat: involvement of oxalate in cold hyperalgesia but not mechanical allodynia. Pain 147:165–174CrossRefPubMed Sakurai M, Egashira N, Kawashiri T, Yano T, Ikesue H, Oishi R (2009) Oxaliplatin-induced neuropathy in the rat: involvement of oxalate in cold hyperalgesia but not mechanical allodynia. Pain 147:165–174CrossRefPubMed
20.
go back to reference Sittl R, Lampert A, Huth T, Schuy ET, Link AS, Fleckenstein J, Alzheimer C, Grafe P, Carr RW (2012) Anticancer drug oxaliplatin induces acute cooling-aggravated neuropathy via sodium channel subtype Na(V)1.6-resurgent and persistent current. Proc Natl Acad Sci U S A 109:6704–6709CrossRefPubMedPubMedCentral Sittl R, Lampert A, Huth T, Schuy ET, Link AS, Fleckenstein J, Alzheimer C, Grafe P, Carr RW (2012) Anticancer drug oxaliplatin induces acute cooling-aggravated neuropathy via sodium channel subtype Na(V)1.6-resurgent and persistent current. Proc Natl Acad Sci U S A 109:6704–6709CrossRefPubMedPubMedCentral
21.
go back to reference Ta LE, Espeset L, Podratz J, Windebank AJ (2006) Neurotoxicity of oxaliplatin and cisplatin for dorsal root ganglion neurons correlates with platinum-DNA binding. Neurotoxicology 27:992–1002CrossRefPubMed Ta LE, Espeset L, Podratz J, Windebank AJ (2006) Neurotoxicity of oxaliplatin and cisplatin for dorsal root ganglion neurons correlates with platinum-DNA binding. Neurotoxicology 27:992–1002CrossRefPubMed
22.
go back to reference Peters CM, Jimenez-Andrade JM, Kuskowski MA, Ghilardi JR, Mantyh PW (2007) An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administration of paclitaxel in the rat. Brain Res 1168:46–59CrossRefPubMedPubMedCentral Peters CM, Jimenez-Andrade JM, Kuskowski MA, Ghilardi JR, Mantyh PW (2007) An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administration of paclitaxel in the rat. Brain Res 1168:46–59CrossRefPubMedPubMedCentral
23.
go back to reference Jamieson SM, Liu J, Connor B, McKeage MJ (2005) Oxaliplatin causes selective atrophy of a subpopulation of dorsal root ganglion neurons without inducing cell loss. Cancer Chemother Pharmacol 56:391–399CrossRefPubMed Jamieson SM, Liu J, Connor B, McKeage MJ (2005) Oxaliplatin causes selective atrophy of a subpopulation of dorsal root ganglion neurons without inducing cell loss. Cancer Chemother Pharmacol 56:391–399CrossRefPubMed
24.
go back to reference Tatsushima Y, Egashira N, Kawashiri T, Mihara Y, Yano T, Mishima K, Oishi R (2011) Involvement of substance P in peripheral neuropathy induced by paclitaxel but not oxaliplatin. J Pharmacol Exp Ther 337:226–235CrossRefPubMed Tatsushima Y, Egashira N, Kawashiri T, Mihara Y, Yano T, Mishima K, Oishi R (2011) Involvement of substance P in peripheral neuropathy induced by paclitaxel but not oxaliplatin. J Pharmacol Exp Ther 337:226–235CrossRefPubMed
25.
go back to reference Argyriou AA, Bruna J, Marmiroli P, Cavaletti G (2012) Chemotherapy-induced peripheral neurotoxicity (CIPN): an update. Crit Rev Oncol Hematol 82:51–77CrossRefPubMed Argyriou AA, Bruna J, Marmiroli P, Cavaletti G (2012) Chemotherapy-induced peripheral neurotoxicity (CIPN): an update. Crit Rev Oncol Hematol 82:51–77CrossRefPubMed
26.
go back to reference Argyriou AA, Polychronopoulos P, Iconomou G, Chroni E, Kalofonos HP (2008) A review on oxaliplatin-induced peripheral nerve damage. Cancer Treat Rev 34:368–377CrossRefPubMed Argyriou AA, Polychronopoulos P, Iconomou G, Chroni E, Kalofonos HP (2008) A review on oxaliplatin-induced peripheral nerve damage. Cancer Treat Rev 34:368–377CrossRefPubMed
27.
28.
go back to reference Podratz JL, Knight AM, Ta LE, Staff NP, Gass JM, Genelin K, Schlattau A, Lathroum L, Windebank AJ (2011) Cisplatin induced mitochondrial DNA damage in dorsal root ganglion neurons. Neurobiol Dis 41:661–668CrossRefPubMed Podratz JL, Knight AM, Ta LE, Staff NP, Gass JM, Genelin K, Schlattau A, Lathroum L, Windebank AJ (2011) Cisplatin induced mitochondrial DNA damage in dorsal root ganglion neurons. Neurobiol Dis 41:661–668CrossRefPubMed
29.
go back to reference Argyriou AA, Koltzenburg M, Polychronopoulos P, Papapetropoulos S, Kalofonos HP (2008) Peripheral nerve damage associated with administration of taxanes in patients with cancer. Crit Rev Oncol Hematol 66:218–228CrossRefPubMed Argyriou AA, Koltzenburg M, Polychronopoulos P, Papapetropoulos S, Kalofonos HP (2008) Peripheral nerve damage associated with administration of taxanes in patients with cancer. Crit Rev Oncol Hematol 66:218–228CrossRefPubMed
30.
go back to reference Alejandro LM, Behrendt CE, Chen K, Openshaw H, Shibata S (2013) Predicting acute and persistent neuropathy associated with oxaliplatin. Am J Clin Oncol 36:331–337CrossRefPubMedPubMedCentral Alejandro LM, Behrendt CE, Chen K, Openshaw H, Shibata S (2013) Predicting acute and persistent neuropathy associated with oxaliplatin. Am J Clin Oncol 36:331–337CrossRefPubMedPubMedCentral
31.
go back to reference Argyriou AA, Cavaletti G, Briani C, Velasco R, Bruna J, Campagnolo M, et al. (2013) Clinical pattern and associations of oxaliplatin acute neurotoxicity: a prospective study in 170 patients with colorectal cancer. Cancer 119:438–444CrossRefPubMed Argyriou AA, Cavaletti G, Briani C, Velasco R, Bruna J, Campagnolo M, et al. (2013) Clinical pattern and associations of oxaliplatin acute neurotoxicity: a prospective study in 170 patients with colorectal cancer. Cancer 119:438–444CrossRefPubMed
32.
go back to reference Park SB, Goldstein D, Lin CS, Krishnan AV, Friedlander ML, Kiernan MC (2009) Acute abnormalities of sensory nerve function associated with oxaliplatin-induced neurotoxicity. J Clin Oncol 27:1243–1249CrossRefPubMed Park SB, Goldstein D, Lin CS, Krishnan AV, Friedlander ML, Kiernan MC (2009) Acute abnormalities of sensory nerve function associated with oxaliplatin-induced neurotoxicity. J Clin Oncol 27:1243–1249CrossRefPubMed
33.
go back to reference Velasco R, Bruna J, Briani C, Argyriou AA, Cavaletti G, Alberti P, et al. (2014) Early predictors of oxaliplatin-induced cumulative neuropathy in colorectal cancer patients. J Neurol Neurosurg Psychiatry 85:392–398CrossRefPubMed Velasco R, Bruna J, Briani C, Argyriou AA, Cavaletti G, Alberti P, et al. (2014) Early predictors of oxaliplatin-induced cumulative neuropathy in colorectal cancer patients. J Neurol Neurosurg Psychiatry 85:392–398CrossRefPubMed
34.
go back to reference Moreau P et al. (2011) Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol 12(5):431–440CrossRefPubMed Moreau P et al. (2011) Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol 12(5):431–440CrossRefPubMed
Metadata
Title
Comparison of oxaliplatin and paclitaxel-induced neuropathy (Alliance A151505)
Authors
Deirdre R. Pachman
Rui Qin
Drew Seisler
Ellen M. Lavoie Smith
Suneetha Kaggal
Paul Novotny
Kathryn J. Ruddy
Jacqueline M. Lafky
Lauren E. Ta
Andreas S. Beutler
Nina D. Wagner-Johnston
Nathan P. Staff
Axel Grothey
Patrick M. Dougherty
Guido Cavaletti
Charles L. Loprinzi
Publication date
01-12-2016
Publisher
Springer Berlin Heidelberg
Published in
Supportive Care in Cancer / Issue 12/2016
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-016-3373-1

Other articles of this Issue 12/2016

Supportive Care in Cancer 12/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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