Purpose. Up to 80% of patients undergoing taxanes or platinum-based chemotherapy (CT) develop a disturbing peripheral polyneuropathy referred to as CIPN, that affects their treatment compliance to CT and long-term quality of life (QoL). Cumulative evidence shows that taxanes and platinum agents sensitize epidermal nociceptive terminals by potentiating the activity of nociceptor thermosensitive channels. Our aim was to evaluate the efficacy and safety of a non-pharmacological nociceutical formulation acting on epidermal nociceptive endings preventing, delaying and/or lessening CIPN sensory symptoms during CT. Methods: We designed a proof-of-concept, double-blind, randomized, two-arms multicenter clinical study (NCT06733545). Participants started a daily topical application of the assigned formulation in hands (moisturizing or nociceutical). Upon appearance of neuropathic symptoms in hands and/or feet, they applied the creams twice daily in hands and feet. Diagnosis and follow up of CIPN grade and adverse effects were conducted by study investigators, as well as a QoL questionnaire. Results. A cohort of 142 patients treated with taxanes and/or platinum agents were randomly assigned to the two groups. Withdrawals were similar in both arms (9 and 14), leading to a balanced number of patients per group (61 moisturizing vs 58 nociceutical). Overall, a similar number of participants developed a peripheral neuropathy in both arms (73% moisturizing vs 67% nociceutical, p=0.1). A lower CIPN incidence in hands was observed in the nociceutical arm (32% vs 13%, p=0.03). Furthermore, the nociceutical formulation delayed the appearance of neuropathic symptoms as compared to the moisturizing cream (6 vs 8 cycle, p=0.009). The Leonard scale questionnaire revealed that the nociceutical formulation attenuated the severity of patients neuropathic symptoms from extremely to hardly any (58% vs. 35%, p<0.0017), increasing patient QoL. Conclusion. This pilot study suggests that topical protection of nociceptive epidermal terminals with a topical nociceutical formulation reduced the incidence of CIPN in hands, delayed its onset and increased the QoL of patients. These findings provide solid evidence for a larger, confirmatory clinical study.

CFH and MGE are employees and shareholders of Prospera Biotech. AFC and AFM are inventors of patent EP3621950B1 protecting a family of non-pungent vanilloid analogs, and shareholders and members of the board of Prospera Biotech.

NCT06733545

This study is part of the RDI project (PROMETEO/2021/031) funded by the Generalitat Valenciana; and part of the RDI project PID2021-126423OB-C21 funded by MICIU/AEI/10.13039/501100011033 and FEDER, UE to AFM and AFC.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The protocol was first approved by the Ethics Committee of the Hospital General Universitario de Elche (FISABIO) and, thereafter by the Ethics Committees of all participating Hospitals approved the protocol and the informed consent documents.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

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Data will be shared upon request to Antonio Ferrer-Montiel.