Oxaliplatin‐induced neuropathy after total neoadjuvant therapy for rectal cancer: Dose–response relationship and impact on quality of life

Oxaliplatin-based regimens are increasingly used in total neoadjuvant therapy (TNT) for locally advanced rectal cancer, frequently causing dose-limiting chemotherapy-induced peripheral neuropathy (CIPN), whose extent and impact on health-related quality of life (HrQoL) remain insufficiently characterized. The optimal duration and intensity of chemotherapy within TNT for tumor response and toxicity remain unclear. This retrospective multicenter study (DRKS00033000) assessed the dose-response relationship of CIPN with cumulative oxaliplatin dose (cOXAd) and its impact on HrQoL. A total of 227 patients (164 men) with a median age of 63 (Q1-Q3: 54-68) years, who underwent oxaliplatin-based TNT between 2015 and 2024, were analyzed. HrQoL was assessed cross-sectionally during follow-up using the EORTC QLQ-C30 and QLQ-CIPN20 questionnaires. Multivariable logistic regression was applied to evaluate the relationship between cOXAd and CIPN grade ≥2, and known-group comparisons examined differences in HrQoL scores. At follow-up, 61 patients (26.9%) experienced CIPN grade ≥2 after a median cOXAd of 758.8 mg/m<sup>2</sup>. Higher cOXAd was associated with an increased likelihood of CIPN grade ≥2 (adjusted OR 1.004, 95% CI: 1.002-1.007), corresponding to a 7.8% higher probability per additional FOLFOX cycle (+85 mg/m<sup>2</sup> cOXAd). Patients with CIPN grade ≥2 reported lower mean QLQ-C30 Global Health Scores and Summary Scores (-13.0 and -12.4 points; Cohen's d = -0.59 and -0.68) and higher QLQ-CIPN20 Summary Scores (+23.9 points; Cohen's d = 1.65) compared to those without CIPN. These findings indicate that CIPN is a common dose-dependent toxicity of oxaliplatin-based TNT, associated with considerably reduced HrQoL and markedly increased neuropathy-related symptom burden at follow-up.

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Journal
International Journal of Cancer
Published
2026-02-18
DOI
https://doi.org/10.1002/ijc.70396
Primary Topic
Cancer Treatment and Pharmacology
Type
article
Field-Weighted Citation Impact
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article

Oxaliplatin‐induced neuropathy after total neoadjuvant therapy for rectal cancer: Dose–response relationship and impact on quality of life

Marcel Büttner, Samuel Vorbach, Alexander Fabian, Melanie Schneider et al.
International Journal of Cancer
Cancer Treatment and Pharmacology
article

Oxaliplatin‐induced neuropathy after total neoadjuvant therapy for rectal cancer: Dose–response relationship and impact on quality of life

Marcel Büttner, Samuel Vorbach, Alexander Fabian, Melanie Schneider, Maximilian Römer, Adrianna Cieślak, Christopher Keßler, Jörg Kaufmann, Simon Trommer, Markus Diefenhardt, Klaus Pietschmann, Elgin Hoffmann, J. Beier, Julian Hlouschek, Fabian Schunn, Alina Depardon, Jan‐Niklas Becker, Hai Minh Ha, Daphne Schepers von Ohlen, Maike Trommer, Bernd Frerker, Florian Rißner, Kynann Aninditha, Alexander Rühle, Maria‐Elena von Gruben, Andreas Hinz, Simone Ferdinandus, Felix Ehret, Georg W. Wurschi
article en

Abstract

Oxaliplatin-based regimens are increasingly used in total neoadjuvant therapy (TNT) for locally advanced rectal cancer, frequently causing dose-limiting chemotherapy-induced peripheral neuropathy (CIPN), whose extent and impact on health-related quality of life (HrQoL) remain insufficiently characterized. The optimal duration and intensity of chemotherapy within TNT for tumor response and toxicity remain unclear. This retrospective multicenter study (DRKS00033000) assessed the dose-response relationship of CIPN with cumulative oxaliplatin dose (cOXAd) and its impact on HrQoL. A total of 227 patients (164 men) with a median age of 63 (Q1-Q3: 54-68) years, who underwent oxaliplatin-based TNT between 2015 and 2024, were analyzed. HrQoL was assessed cross-sectionally during follow-up using the EORTC QLQ-C30 and QLQ-CIPN20 questionnaires. Multivariable logistic regression was applied to evaluate the relationship between cOXAd and CIPN grade ≥2, and known-group comparisons examined differences in HrQoL scores. At follow-up, 61 patients (26.9%) experienced CIPN grade ≥2 after a median cOXAd of 758.8 mg/m<sup>2</sup>. Higher cOXAd was associated with an increased likelihood of CIPN grade ≥2 (adjusted OR 1.004, 95% CI: 1.002-1.007), corresponding to a 7.8% higher probability per additional FOLFOX cycle (+85 mg/m<sup>2</sup> cOXAd). Patients with CIPN grade ≥2 reported lower mean QLQ-C30 Global Health Scores and Summary Scores (-13.0 and -12.4 points; Cohen's d = -0.59 and -0.68) and higher QLQ-CIPN20 Summary Scores (+23.9 points; Cohen's d = 1.65) compared to those without CIPN. These findings indicate that CIPN is a common dose-dependent toxicity of oxaliplatin-based TNT, associated with considerably reduced HrQoL and markedly increased neuropathy-related symptom burden at follow-up.

International Journal of Cancer
Goethe University Frankfurt (DE), Innsbruck Medical University (AT), Universität Hamburg (DE), University of Freiburg (DE), German Cancer Research Center (DE), University of Bremen (DE), Friedrich-Alexander-Universität Erlangen-Nürnberg (DE), Universität Innsbruck (AT), Johannes Gutenberg University Mainz (DE), Heidelberg University (DE), University Medical Center Freiburg (DE), University Hospital Heidelberg (DE), TUM Klinikum (DE), Medizinische Hochschule Hannover (DE), Humboldt-Universität zu Berlin (DE), Universitätsklinikum Erlangen (DE), Düsseldorf University Hospital (DE), University Medical Center of the Johannes Gutenberg University Mainz (DE), Integrated Oncology (United States) (US), German Cancer Society (DE), Ernst Abbe University of Applied Sciences Jena (DE), University Hospital Schleswig-Holstein (DE), Essen University Hospital (DE), University Children's Hospital Tübingen (DE), University Hospital Leipzig (DE), Technical University of Applied Sciences Lübeck (DE), University Hospital Frankfurt (DE), Jena University Hospital (DE), Saxon Institute for Applied Biotechnology (DE), University Hospital in Halle (DE), University Hospital Cologne (DE), University Medical Centre Mannheim (DE), Frankfurt Cancer Institute (DE), Klinikum Stuttgart (DE), West German Heart and Vascular Center Essen (DE), University Hospital Carl Gustav Carus (DE), Heinrich Heine University Düsseldorf (DE), University of Rostock (DE), Leipzig University (DE), University of Lübeck (DE), Otto-von-Guericke-Universität Magdeburg (DE)
Universitätsklinikum Jena
Openalex Percentile: Top 50%
Cancer Treatment and Pharmacology
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