Oxaliplatin-induced peripheral neuropathy as a factor influencing the efficacy of the mFOLFOX6 regimen in patients with metastatic colorectal cancer: a retrospective study

Natalenko S.A., Orlova R.V., Belyak N.P., Kutukova S.I., Ksanaeva L.A.

1) City Clinical Oncology Dispensary, St. Petersburg, Russia; 2) St. Petersburg State University, St. Petersburg, Russia; 3) Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia

Background: Oxaliplatin is an important component of first-line chemotherapy (CT) regimens for metastatic colorectal cancer (mCRC), but its use is often limited by the development of peripheral neuropathy (PN). The optimal relative dose intensity (RDI) that achieves a balance between efficacy and toxicity remains unresolved.
Objective: Evaluation of the effect of oxaliplatin RDI on the incidence of PN and treatment response rates in patients with mCRC.
Materials and methods: A retrospective, single-center cohort study was conducted. Electronic medical records of 142 patients with mCRC receiving CT using the mFOLFOX6 regimen were included. The effect of oxaliplatin RDI on the development of neuropathy (grade ≥2), objective response rate, progression-free survival (PFS), and overall survival (OS) was assessed. The association was assessed using logistic regression, Kaplan-Meier analysis, and ROC analysis. The median follow-up was 36 months.
Results: An RDI ≥78.9% was significantly associated with a higher incidence of oxaliplatin-induced grade ≥2 PN (OR=8.25, 95% CI: 2.56–26.62; p=0.0004). No effect of high dose intensity on PFS (OR=1.24; p=0.276) and OS (OR=0.87; p=0.561) was found, as was the effect on the objective response rate.
Conclusion: A higher oxaliplatin RDI is associated with an increased risk of neuropathy but does not improve survival, supporting the rationale for individual dose reduction.

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About the Authors

Sofia A. Natalenko, Postgraduate Student, Department of Oncology, Medical Institute, St. Petersburg State University; Oncologist, Department of Antitumor Drug Therapy No. 10, St. Petersburg City Clinical Oncology Dispensary, St. Petersburg, Russia; 79818438953@yandex.ru, ORCID:
https://orcid.org/0009-0002-2823-3482, SPIN: 8636-2022
R.V. Orlova, Dr. Sci. (Med.), Professor, Head of the Oncology Department, Medical Institute, St. Petersburg State University; Chief Specialist in Clinical Oncology, City Clinical Oncology Dispensary, St. Petersburg, Russia; orlova_rashida@mail.ru, ORCID: https://orcid.org/0000-0003-4447-9458, SPIN: 3480-2098, Author ID 401170
S.I. Kutukova, Dr. Sci. (Med.), Professor, Department of Dentistry, Surgical and Maxillofacial Surgery; Associate Professor, Department of Oncology, Faculty of Postgraduate Education, Pavlov First Saint Petersburg State Medical University; Oncologist, Department of Antitumor Drug Therapy No. 10, City Clinical Oncology Dispensary, St. Petersburg, Russia; dr.s.kutukova@gmail.com, ORCID: https://orcid.org/0000-0003-2221-4088, SPIN-code: 6735-6556, Author ID: 698363
N.P. Belyak, Cand. Sci. (Med.), Associate Professor, Department of Oncology, Medical Institute, Saint Petersburg State University; Head of Department of Antitumor Drug Therapy No. 10, City Clinical Oncology Dispensary, Saint Petersburg, Russia; drnpb@mail.ru, ORCID:
https://orcid.org/0000-0003-0402-6067, SPIN: 2937-4858, Author ID 778562
L.A. Ksanaeva, Oncologist, Department of Antitumor Drug Therapy No. 10, City Clinical Oncology Dispensary, St. Petersburg, Russia;
leila.ksanaeva@gmail.com; ORCID: https://orcid.org/0009-0003-6381-3076

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