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Randomized adaptive selection trial of cryotherapy, compression therapy, and placebo to prevent taxane-induced peripheral neuropathy in patients with breast cancer

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Abstract

Background

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating adverse effect of taxane therapy. Small non-randomized studies in patients with early-stage breast cancer (ESBC) suggest both cryotherapy and compression therapy may prevent CIPN. It is unknown which is more effective.

Methods

We conducted a randomized phase IIB adaptive sequential selection trial of cryotherapy vs. compression therapy vs. placebo (“loose” gloves/socks) during taxane chemotherapy. Participants were randomized in triplets. Garments were worn for 90–120 min, beginning 15 min prior and continuing for 15 min following the infusion. The primary goal was to select the best intervention based on a Levin–Robbins–Leu sequential selection procedure. The primary endpoint was a < 5-point decrease in the Functional Assessment of Cancer Therapy Neurotoxicity (FACT-NTX) at 12 weeks. An arm was eliminated if it had four or more fewer successes than the currently leading arm. Secondary endpoints included intervention adherence and patient-reported comfort/satisfaction.

Results

Between April 2019 and April 2021, 63 patients were randomized (cryotherapy (20); compression (22); placebo (21)). Most patients (60.3%) were treated with docetaxel. The stopping criterion was met after the 17th triplet (n = 51) was evaluated; success at 12 weeks occurred in 11 (64.7%) on compression therapy, 7 (41.1%) on cryotherapy, and 7 (41.1%) on placebo. Adherence to the intervention was lowest with cryotherapy (35.0%) compared to compression (72.7%) and placebo (76.2%).

Conclusion

Compression therapy was the most effective intervention in this phase IIB selection trial to prevent CIPN and was well tolerated. Compression therapy for the prevention of CIPN should be evaluated in a phase III study.

Clinical trial registration

ClinicaTrials.gov Identifier: NCT03873272.

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Data availability

Data are available from the authors upon reasonable request and permission from the Columbia University Medical Center.

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Funding

This research was funded by the National Cancer Institute NIH/NCI 1R03CA238982-01A1 (MA) and the Thompson Family Foundation Initiative at Columbia University. Study garments were donated by Sigvaris and NatraCure.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA

    Melissa K. Accordino, Meghna S. Trivedi, Katherine D. Crew, Khadija Faheem, Erik Harden, Alessandra Taboada, Elisabeth Larson, Erin Honan, Cynthia Law & Dawn L. Hershman

  2. Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 161 Ft Washington Ave #1071, New York, NY, 212-305-1945, USA

    Melissa K. Accordino, Shing Lee, Meghna S. Trivedi, Katherine D. Crew, Rohit Raghunathan, Khadija Faheem, Erik Harden, Alessandra Taboada, Elisabeth Larson, Erin Honan, Cynthia Law & Dawn L. Hershman

  3. Department of Biostatistics, Columbia University Medical Center, New York, NY, USA

    Shing Lee, Cheng Shiun Leu, Bruce Levin, Rohit Raghunathan & Lauren Franks

  4. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Kevin Kalinsky

  5. Deparment of Medicine, Columbia University Medical Center, New York, NY, USA

    Beatriz Desanti de Oliveira

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  1. Melissa K. Accordino
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Corresponding author

Correspondence to Melissa K. Accordino.

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Conflict of interest

Kevin Kalinsky has the following conflicts of interest: Advisory/Consulting: Genetech/Roche, Immunomedics, Seattle Genetics, Onosec, 4D pharm, Daiich Sankyo, Puma Biotechnology, Mersna, Menairini Silicon Biosystems, Myovant Sciences, Takeda; and from spouse: Stock in EQRX, Grail, Array BioPharma, and Pfizer (Prior Employee).

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Accordino, M.K., Lee, S., Leu, C.S. et al. Randomized adaptive selection trial of cryotherapy, compression therapy, and placebo to prevent taxane-induced peripheral neuropathy in patients with breast cancer. Breast Cancer Res Treat 204, 49–59 (2024). https://doi.org/10.1007/s10549-023-07172-y

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