Fingolimod for treatment and or prevention of chemotherapy-induced peripheral neuropathy in humans?

Abstract

Purpose: Substantial preclinical data support that fingolimod, a drug that dysregulates sphingolipid metabolism, could both prevent chemotherapy-induced neuropathy (CIPN) and treat established chemotherapy-induced neuropathy. Methods: Two pilot-phase clinical trials were developed to evaluate whether fingolimod could 1) inhibit the development of paclitaxel-induced peripheral neuropathy and 2) diminish established CIPN in humans. Results: Unfortunately, both clinical trials were not able to fulfill planned accrual goals. One of the major accrual problems was the requirement for patients to be in the clinic for 8 hours following their first oral dose of fingolimod. The prevention of paclitaxel CIPN trial accrued 2 patients, one of whom did very well without any significant CIPN while the other patient developed CIPN that led to early paclitaxel dose cessation. The treatment of established CIPN trial accrued 7 of 10 planned patients. The results from the 6 patients who started daily treatment with fingolimod did not suggest that it substantially decreased CIPN over what might have been expected from a placebo effect. Conclusion: Fingolimod is a clinically difficult treatment for patients to start and the limited clinical data from these protocols did not support that it was able to prevent CIPN or treat established CIPN.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

NCT03943498 and NCT03941743

Funding Statement

NCI funds provided to the Alliance cooperative oncology group

Author Declarations

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:

IRB of Mayo Clinic gave ethical approval for this work

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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Yes

Data Availability

All data produced in the present work are contained in the manuscript

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