Bernardino Clavo, Ángeles Cánovas-Molina, Mario Federico, Gregorio Martínez-Sánchez, Gretel Benítez, Saray Galván, Yolanda Ramallo-Fariña, Himar Fabelo, Sara Cazorla-Rivero, Elba Lago-Moreno, Carla Antonilli, Juan A. Díaz-Garrido, Ignacio J. Jorge, Gustavo Marrero-Callico, Delvys Rodríguez-Abreu, Francisco Rodríguez Esparragón.

SIMPLE SUMARY

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy. CIPN can lead to a dose reduction and/or the interruption of chemotherapy, limiting its effectiveness, while chronic CIPN decreases patients’ quality of life. Unfortunately, the only evidence-based treatment for CIPN-related pain, duloxetine, provides only a modest clinical benefit, and there is no effective clinical management option for numbness and tingling. This narrative review summarizes the mechanisms underlying CIPN and the effects of ozone. It also summarizes experimental studies (18) and clinical reports (27) published between 1995 and 2025 that offer preliminary evidence supporting the potential role of ozone treatment in managing CIPN and highlight the need for ongoing randomized clinical trials to establish its efficacy.

ABSTRACT

Background:

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy. CIPN can lead to a dose reduction and/or the interruption of chemotherapy, limiting its effectiveness, while chronic CIPN decreases patients’ quality of life. Improvements in cancer treatment and patients’ survival have increased the number of patients living with CIPN. The only evidence-based treatment for CIPN-related pain, duloxetine, provides only modest clinical benefit, and there is no effective clinical management option for numbness and tingling. Several experimental studies and clinical reports suggest that adjuvant ozone treatment may be beneficial in managing CIPN.

Methods:

This narrative review aims to provide an overview of current knowledge regarding CIPN and ozone therapy. Specifically, it summarizes experimental studies (18) and clinical reports (27) published between 1995 and 2025 that offer preliminary evidence supporting the potential role of ozone treatment in managing CIPN, highlighting the need for ongoing randomized clinical trials to establish its efficacy. Additionally, this review highlights existing gaps in the literature and proposes directions for future research.

Results:

The hypothesized mechanisms of action and experimental findings suggest that ozone therapy may be a valuable intervention for CIPN, a concept supported by preliminary clinical observations.

Conclusions:

Clinically relevant approaches for established CIPN are currently unavailable. While preliminary data suggest a potential role of ozone therapy, clinical evidence remains limited. Further high-quality randomized controlled trials are needed to confirm its efficacy and safety in this context; several trials are currently ongoing.

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