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Clinical Trial
. 2024 Feb;204(1):49-59.
doi: 10.1007/s10549-023-07172-y. Epub 2023 Dec 7.

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

Melissa K Accordino  1   2 , Shing Lee  3   4 , Cheng Shiun Leu  4 , Bruce Levin  4 , Meghna S Trivedi  5   3 , Katherine D Crew  5   3 , Kevin Kalinsky  6 , Rohit Raghunathan  3   4 , Khadija Faheem  5   3 , Erik Harden  5   3 , Alessandra Taboada  5   3 , Beatriz Desanti de Oliveira  7 , Elisabeth Larson  5   3 , Lauren Franks  4 , Erin Honan  5   3 , Cynthia Law  5   3 , Dawn L Hershman  5   3
Affiliations
Clinical Trial

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

Melissa K Accordino et al. Breast Cancer Res Treat. 2024 Feb.

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.

Keywords: Chemotherapy-induced peripheral neuropathy; Compression therapy; Cryotherapy; Taxane chemotherapy.

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Conflict of interest statement

Conflicts of Interest: Kevin Kalinksy: Advisory/Consulting: Genentech/Roche, Immunomedics, Seattle Genetics, Oncosec, 4D pharma, Daiichi Sankyo, Puma Biotechnology, Mersna, Menarini Silicon Biosystems, Myovant Sciences, Takeda. Spouse: Stock: EQRX; Grail, Array BioPharma and Pfizer (Prior Employee)

Figures

Figure 1:
Figure 1:. Flowchart of Patients in the CONTRoL Trial.
CONSORT diagram, 72 patients were screened and 63 patients were included in the analysis. During the study period three patients died (unrelated to study-treatment), two patients died prior to the week-12 assessment and one patient died prior to the week-24 assessment.,
Figure 2:
Figure 2:. Percentage of Patients who Endorse Satisfaction with Study Interventions (1-4 Likert) Scale at week-12 (n=53) and week-24 (n=45)
The percentage of patients who endorse each category of patient reported satisfaction (x-axis) with assigned study garments, the right side (blue) indicates satisfaction and the left side (red) indicates dissatisfaction. At 12-weeks, 90.5% reported being satisfied/very satisfied with the study garments in the compression arm, compared to 75.0% treated with cryotherapy, and 93.8% treated with placebo.
Figure 3
Figure 3
A: Worsening CTCAE Toxicities Related to Taxane-Chemotherapy From Baseline to 12-Weeks (n=63) Figure 3B: Worsening CTCAE Toxicities Related to Taxane-Chemotherapy From Baseline to 24-Weeks (n=63) The percentage of patients in each study arm with worsening from baseline CTCAE toxicities related to taxane-chemotherapy including: peripheral sensory neuropathy, paresthesia, dysesthesia, neuralgia, and peripheral motor neuropathy, at (A) 12-week and (B) 24-weeks.
Figure 3
Figure 3
A: Worsening CTCAE Toxicities Related to Taxane-Chemotherapy From Baseline to 12-Weeks (n=63) Figure 3B: Worsening CTCAE Toxicities Related to Taxane-Chemotherapy From Baseline to 24-Weeks (n=63) The percentage of patients in each study arm with worsening from baseline CTCAE toxicities related to taxane-chemotherapy including: peripheral sensory neuropathy, paresthesia, dysesthesia, neuralgia, and peripheral motor neuropathy, at (A) 12-week and (B) 24-weeks.
See this image and copyright information in PMC

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