Comparison of nab-paclitaxel, paclitaxel, and oxaliplatin-induced peripheral neuropathy: a cross-sectional cohort study
DOI:
https://doi.org/10.2340/1651-226X.2025.42935Keywords:
Cancer survivorship, chemotherapy-induced peripheral neuropathy, cohort study, toxicityAbstract
Background and purpose: There remains limited evidence regarding the relative neurotoxic potential of nab-paclitaxel long-term. This cross-sectional matched cohort study aimed to compare the severity and natural history of chemotherapy-induced peripheral neuropathy (CIPN) between patients treated with nab-paclitaxel and patients treated with oxaliplatin or paclitaxel using a suite of clinical, patient reported, and neurophysiological assessments.
Patients and methods: CIPN assessments included the total neuropathy score (TNSc), grooved pegboard assessment, sensory assessments (grating orientation task and Von-Frey assessment), patient-reported outcome measures, and neurophysiological studies. The matched cohort included 72 patients (24 nab-paclitaxel, 24 paclitaxel, and 24 oxaliplatin); each stratified into two groups by time post-treatment, 0–4 months, and > 6 months.
Results: Chronic neuropathy was reported by 71% of nab-paclitaxel-treated patients, most prominently numbness in the lower limbs. Longer time post-treatment was associated with significantly better TNSc scores (p = 0.044). Neuropathy severity was similar for nab-paclitaxel and paclitaxel. Neuropathy severity was worse for oxaliplatin compared to nab-paclitaxel, as measured by sensory function (p < 0.05) and sural amplitude (p = 0.003), but similar for patient-reported and neurological-graded assessments.
Interpretation: These findings underscore the importance of inclusion of a range of multimodal CIPN assessments to characterize relative burden of toxicity between chemotherapy agents. CIPN severity was similar between nab-paclitaxel and paclitaxel cohorts, but more severe in oxaliplatin-treated patients.
Downloads
References
Park SB, Goldstein D, Krishnan AV, Lin CS-Y, Friedlander ML, Cassidy J, et al. Chemotherapy-induced peripheral neurotoxicity: a critical analysis. CA Cancer J Clin. 2013;63:419–37.
https://doi.org/10.3322/caac.21204 DOI: https://doi.org/10.3322/caac.21204
Hertz DL, Childs DS, Park SB, Faithful S, Ke Y, Ali NT, et al. Patient-centric decision framework for treatment alterations in patients with chemotherapy-induced peripheral neuropathy (CIPN). Cancer Treat Rev. 2021;99:102241.
https://doi.org/10.1016/j.ctrv.2021.102241 DOI: https://doi.org/10.1016/j.ctrv.2021.102241
Pachman DR, Qin R, Seisler D, Smith EML, Kaggal S, Novotny P, et al. Comparison of oxaliplatin and paclitaxel-induced neuropathy (Alliance A151505). Support Care Cancer. 2016;24:5059–68.
https://doi.org/10.1007/s00520-016-3373-1 DOI: https://doi.org/10.1007/s00520-016-3373-1
Timmins HC, Li T, Trinh T, Kiernan MC, Harrison M, Boyle F, et al. Weekly paclitaxel-induced neurotoxicity in breast cancer: outcomes and dose response. Oncologist. 2021;26(5):366–74.
https://doi.org/10.1002/onco.13697 DOI: https://doi.org/10.1002/onco.13697
Goldstein D, Von Hoff DD, Moore M, Greeno E, Tortora G, Ramanathan RK, et al. Development of peripheral neuropathy and its association with survival during treatment with nab-paclitaxel plus gemcitabine for patients with metastatic adenocarcinoma of the pancreas: a subset analysis from a randomised phase III trial (MPACT). Eur J Cancer. 2016;52:85–91.
https://doi.org/10.1016/j.ejca.2015.10.017 DOI: https://doi.org/10.1016/j.ejca.2015.10.017
Guo X, Sun H, Dong J, Feng Y, Li H, Zhuang R, et al. Does nab-paclitaxel have a higher incidence of peripheral neuropathy than solvent-based paclitaxel? Evidence from a systematic review and meta-analysis. Crit Rev Oncol Hematol. 2019;139:16–23.
https://doi.org/10.1016/j.critrevonc.2019.04.021 DOI: https://doi.org/10.1016/j.critrevonc.2019.04.021
Peng L, Bu Z, Ye X, Zhou Y, Zhao Q. Incidence and risk of peripheral neuropathy with nab-paclitaxel in patients with cancer: a meta-analysis. Eur J Cancer Care (Engl). 2017;26(5):12407.
https://doi.org/10.1111/ecc.12407 DOI: https://doi.org/10.1111/ecc.12407
Timmins HC, Li T, Huynh W, Kiernan MC, Baron-Hay S, Boyle F, et al. Electrophysiological and phenotypic profiles of taxane-induced neuropathy. Clin Neurophysiol. 2020;131(8):1979–85.
https://doi.org/10.1016/j.clinph.2020.02.028 DOI: https://doi.org/10.1016/j.clinph.2020.02.028
Postma TJ, Aaronson NK, Heimans JJ, Muller MJ, Hildebrand JG, Delattre JY, et al. The development of an EORTC quality of life questionnaire to assess chemotherapy-induced peripheral neuropathy: the QLQ-CIPN20. Eur J Cancer. 2005;41:1135–9.
https://doi.org/10.1016/j.ejca.2005.02.012 DOI: https://doi.org/10.1016/j.ejca.2005.02.012
Binda D, Vanhoutte EK, Cavaletti G, Cornblath DR, Postma TJ, Frigeni B, et al. Rasch-built overall disability scale for patients with chemotherapy-induced peripheral neuropathy (CIPN-R-ODS). Eur J Cancer. 2013;49(13):2910–18.
https://doi.org/10.1016/j.ejca.2013.04.004 DOI: https://doi.org/10.1016/j.ejca.2013.04.004
Schmidt SL, Oliveira RM, Rocha FR, Abreu-Villaca Y. Influences of handedness and gender on the grooved pegboard test. Brain Cognit. 2000;44:445–54.
https://doi.org/10.1006/brcg.1999.1204 DOI: https://doi.org/10.1006/brcg.1999.1204
Craig JC. Grating orientation as a measure of tactile spatial acuity. Somatosens Mot Res. 1999;16:197–206.
https://doi.org/10.1080/08990229970456 DOI: https://doi.org/10.1080/08990229970456
Rolke R, Baron R, Maier C, Tölle TR, Treede DR, Beyer A, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain. 2006;123(3):231–43.
https://doi.org/10.1016/j.pain.2006.01.041 DOI: https://doi.org/10.1016/j.pain.2006.01.041
Cavaletti G, Jann S, Pace A, Plasmati R, Siciliano G, Briani C, et al. Multi-center assessment of the total neuropathy score for chemotherapy-induced peripheral neurotoxicity. J Peripher Nerv Syst. 2006;11:135–41.
https://doi.org/10.1111/j.1085-9489.2006.00078.x DOI: https://doi.org/10.1111/j.1085-9489.2006.00078.x
Cornblath DR, Chaudhry V, Carter K, Lee D, Seysedadr M, Miernicki M, et al. Total neuropathy score: validation and reliability study. Neurology. 1999;53:1660.
https://doi.org/10.1212/WNL.53.8.1660 DOI: https://doi.org/10.1212/WNL.53.8.1660
Liveson JA, Ma DM. Laboratory reference for clinical neurophysiology. Oxford University Press, New York; 1992.
Li T, Timmins HC, Trinh T, Mizrahi D, Harrison M, Horvath LG, et al. Patient-reported outcome measures in chemotherapy-induced peripheral neurotoxicity: defining minimal and clinically important changes. J Natl Compr Canc Netw. 2023;21(2):125–32.e3.
https://doi.org/10.6004/jnccn.2022.7074 DOI: https://doi.org/10.6004/jnccn.2022.7074
Kida K, Yamada A, Shimada K, Narui K, Sugae S, Shimizu D, et al. A prospective comparison study utilizing patient-reported outcomes of taxane-related peripheral neuropathy between nab-paclitaxel and standard paclitaxel in patients with breast cancer. Breast Cancer. 2024;31(3):409–16.
https://doi.org/10.1007/s12282-024-01551-z DOI: https://doi.org/10.1007/s12282-024-01551-z
Tan A, McCrary JM, Park SB, Trinh T, Goldstein D. Chemotherapy-induced peripheral neuropathy-patient-reported outcomes compared with NCI-CTCAE grade. Support Care Cancer. 2019;27(12):4771–7.
https://doi.org/10.1007/s00520-019-04781-6 DOI: https://doi.org/10.1007/s00520-019-04781-6
Hirsh V, Okamoto I, Hon JK, Page RD, Orsini J, Sakai H, et al. Patient-reported neuropathy and taxane-associated symptoms in a phase 3 trial of nab-paclitaxel plus carboplatin versus solvent-based paclitaxel plus carboplatin for advanced non-small-cell lung cancer. J Thorac Oncol. 2014;9:83–90.
https://doi.org/10.1097/JTO.0000000000000011 DOI: https://doi.org/10.1097/JTO.0000000000000011
Deng X, Huang X, Dong X, Mao G, Xing W. Efficacy and safety of nanopaclitaxel formulation for cancer treatment: evidence from randomized clinical trials. Nanomedicine. 2023;18(10):833–43.
https://doi.org/10.2217/nnm-2023-0080 DOI: https://doi.org/10.2217/nnm-2023-0080
Mo H, Yan X, Zhao F, Teng Y, Sun X, Lv Z, et al. Association of taxane type with patient-reported chemotherapy-induced peripheral neuropathy among patients with breast cancer. JAMA Netw Open. 2022;5(11):e2239788.
https://doi.org/10.1001/jamanetworkopen.2022.39788 DOI: https://doi.org/10.1001/jamanetworkopen.2022.39788
McCrary JM, Goldstein D, Trinh T, Timmins HC, Li T, Friedlander M, et al. Optimizing clinical screening for chemotherapy-induced peripheral neuropathy. J Pain Sympt Manag. 2019;58:1023–32.
https://doi.org/10.1016/j.jpainsymman.2019.07.021 DOI: https://doi.org/10.1016/j.jpainsymman.2019.07.021
Alberti P, Rossi E, Cornblath DR, Merkies ISJ, Postma TJ, Frigeni B, et al. Physician-assessed and patient-reported outcome measures in chemotherapy-induced sensory peripheral neurotoxicity: two sides of the same coin. Ann Oncol. 2014;25(1):257–64.
https://doi.org/10.1093/annonc/mdt409 DOI: https://doi.org/10.1093/annonc/mdt409
Li T, Timmins HC, Mahfouz FM, Trinh T, Mizrahi D, Horvath LG, et al. Validity of patient-reported outcome measures in evaluation nerve damage following chemotherapy. JAMA Netw Open. 2024;7(8):e2424139.
https://doi.org/10.1001/jamanetworkopen.2024.24139 DOI: https://doi.org/10.1001/jamanetworkopen.2024.24139
Timmins HC, Li T, Goldstein D, Trinh T, Mizrahi D, Harrison M, et al. The impact of obesity on neuropathy outcomes for paclitaxel- and oxaliplatin-treated cancer survivors. J Cancer Surviv. 2022;16(2):223–32.
https://doi.org/10.1007/s11764-021-01012-y DOI: https://doi.org/10.1007/s11764-021-01012-y
Mizrahi D, Park SB, Li T, Timmins HC, Trinh T, Au K, et al. Hemoglobin, body mass index, and age as risk factors for paclitaxel- and oxaliplatin-induced peripheral neuropathy. JAMA Netw Open. 2021;4(2):e2036695.
https://doi.org/10.1001/jamanetworkopen.2020.36695 DOI: https://doi.org/10.1001/jamanetworkopen.2020.36695
Catalano M, Ramello M, Conca R, Aprile G, Petrioli R, Roviello G. Risk factors for nab-paclitaxel and gemcitabine-induced peripheral neuropathy in patients with pancreatic cancer. Oncology. 2022;100(7):384–91.
https://doi.org/10.1159/000524868 DOI: https://doi.org/10.1159/000524868
Kanbayashi Y, Sakaguchi K, Ishikawa T, Tabuchi Y, Takagi R, Yokota I, et al. Predictors of the development of nab-paclitaxel-induced peripheral neuropathy in breast cancer patients: post hoc analysis of a prospective, phase II, self-controlled clinical trial. Med Oncol. 2022;39(10):153.
https://doi.org/10.1007/s12032-022-01754-4 DOI: https://doi.org/10.1007/s12032-022-01754-4
Hooshmand K, Goldstein D, Timmins HC, Li T, Harrison M, Friedlander ML, et al. Polygenic risk of paclitaxel-induced peripheral neuropathy: a genome-wide association study. J Transl Med. 2022;20(1):564.
https://doi.org/10.1186/s12967-022-03754-4 DOI: https://doi.org/10.1186/s12967-022-03754-4
Argyriou AA, Polychronopoulos P, Iconomou G, Chroni E, Kalofonos HP. A review on oxaliplatin-induced peripheral nerve damage. Cancer Treat Rev. 2008;34:368–77.
https://doi.org/10.1016/j.ctrv.2008.01.003 DOI: https://doi.org/10.1016/j.ctrv.2008.01.003
Battaglini E, Goldstein D, Grimison P, MuCullough S, Mendoza-Jones P, Park SB. Chemotherapy-induced peripheral neurotoxicity in cancer survivors: predictors of long-term patient outcomes. J Natl Compr Canc Netw. 2021;19(7):821–8.
https://doi.org/10.6004/jnccn.2021.7026 DOI: https://doi.org/10.6004/jnccn.2021.7026
Hershman DL, Till C, Wright JD, Awad D, Ramsey SD, Barlow WE, et al. Comorbidities and risk of chemotherapy-induced peripheral neuropathy among participants 65 years or older in Southwest Oncology Group clinical trials. J Clin Oncol. 2016;34(25):3014–22.
https://doi.org/10.1200/JCO.2015.66.2346 DOI: https://doi.org/10.1200/JCO.2015.66.2346
Molassiotis A, Cheng HL, Leung KT, Li YC, Wong KH, Au JSK, et al. Risk factors for chemotherapy-induced peripheral neuropathy in patients receiving taxane- and platinum-based chemotherapy. Brain Behav. 2019;9(6):e01312.
https://doi.org/10.1002/brb3.1312 DOI: https://doi.org/10.1002/brb3.1312
Greenwald MK, Ruterbusch JJ, Beebe-Dimmer JL, Simon MS, Albrecht TL, Schwartz AG. Risk of incident claims for chemotherapy-induced peripheral neuropathy among women with breast cancer in a Medicare population. J Am Canc Soc. 2019;125(2):269–77.
https://doi.org/10.1002/cncr.31798 DOI: https://doi.org/10.1002/cncr.31798
Hines RB, Schoborg C, Sumner T, Thiesfeldt D, Zhang S. The associations of oxaliplatin-induced peripheral neuropathy, sociodemographic characteristics, and clinical characteristics with time to fall in older adults with colorectal cancer. Am J Epidemiol. 2024;193(9):1271–80.
https://doi.org/10.1093/aje/kwae067 DOI: https://doi.org/10.1093/aje/kwae067
Mizrahi D, Goldstein D, Kiernan MC, Robinson L, Pitiyarachchi O, McCullough S, et al. Development and consensus process for a clinical pathway for the assessment and management of chemotherapy-induced peripheral neuropathy. Support Care Cancer. 2022;30:5965–74.
https://doi.org/10.1007/s00520-022-07024-3 DOI: https://doi.org/10.1007/s00520-022-07024-3
Additional Files
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2025 Terry Trinh, Kimberley Au, Arun V. Krishnan, Hannah C. Timmins, Tiffany Li, Peter Grimison, David Goldstein, Susanna B. Park
This work is licensed under a Creative Commons Attribution 4.0 International License.
