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Randomized Controlled Trial
. 2025 Jul 31;33(8):732.
doi: 10.1007/s00520-025-09795-x.

Multi-institutional, randomized, controlled trial to assess the efficacy and tolerability of a reusable, self-contained cryotherapy delivery device

Richard Zuniga  1 , Vikas Dembla  2 , Naheed Alam  3 , Chaitali Nangia  4 , Thomas Guerrero-Garcia  5 , Gina Chung  6 , Ebenezer Kio  7 , Mylene Go  8 , Erev Tubb  9 , Stephen Sonis  10   11 , Frank Jacobucci  12
Affiliations
Randomized Controlled Trial

Multi-institutional, randomized, controlled trial to assess the efficacy and tolerability of a reusable, self-contained cryotherapy delivery device

Richard Zuniga et al. Support Care Cancer. .

Abstract

Purpose: Cryotherapy is an effective mucositis intervention for selected chemotherapy regimens, but reliance on ice chips has limited its applicability. Our objective was to assess the efficacy and tolerability of a reusable, self-contained, device as an alternative delivery mode.

Methods: A total of 164 patients randomized 2:1 received the device (Chemo Mouthpiece; CMP]) + best supportive care (BSC) (arm A) or BSC only (control, arm B), across 16 study sites. Inclusion criteria allowed broad tumor diagnosis and chemotherapy regimens. During the first two cycles of treatment, patients completed daily questionnaires in which they graded oral pain (OP) and analgesic use (AU) to control mouth pain. A questionnaire assessed device tolerability at the trial's end.

Results: The majority of patients received chemotherapy for breast cancer (arm A 52.7%, arm B 61.1%). Colorectal cancers were the next most common diagnosis. The percentage of visits in which any OP (> 0) in cycles 1 and 2 was reported was less among device-using individuals (CMP 17.8% vs Control 24.6%; p < 0.001). Whereas 26% of controls (arm B) required analgesics during their two cycles of treatment, the frequency was 11.3% among arm A (p = 0.01). Arm B AU was reported in 7.7% of visits compared to 1.8% of arm A visits (p < 0.001). End-of-study assessments of device tolerability were favorable.

Conclusions: CMP use for 14 days following chemotherapy infusion mitigated chemotherapy-associated OP and AU. The effect was seen over two cycles of treatment with known stomatotoxic agents having both short and long half-lives. The device was well tolerated.

Trial registration: ClinicalTrials.gov (NCT04595838) Posted August 31, 2020.

Keywords: Breast cancer; Chemotherapy; Cryotherapy; Device; Oral mucositis.

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Conflict of interest statement

Declarations. Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki and reviewed and approved by regional (WIRB-Copernicus Group IRB) or institutional IRBs. Additional Information: Preliminary results of portions of this trial were presented as an abstract at the 2024 Annual Meeting of MASCC held in Lille, France; Supportive Care in Cancer (2024) 32 (Suppl 1):S434. Competing interests: RZ is a consultant for Mirati Therapeutics, Flatiron and Bristol-Myers Squibb (BMS) and has received research and travel support from ChemoMouthpiece, LLC; VD participates in a Speaker Bureau for BMS/Regeneron and has equity in BMS; NA, GC, CN, EK, ET, MG, TG have no conflicts to declare; FJ is an employee of ChemoMouthpiece; SS is an employee of Biomodels, LLC and Primary Endpoint Solutions, LLC. Both companies assist industry (including ChemoMouthpiece), government and academics to study and enable drugs, biologicals, and devices to treat patients for a variety of indications including cancer and side effects and toxicities of its treatment.

Figures

Fig. 1
Fig. 1
Chemo mouthpiece device. The device consists of an outer clear chamber prefilled with a proprietary saline solution with the inner, blue chamber prefilled with filtered water. Once filled by the manufacturer, the device does not require refilling
Fig. 2
Fig. 2
Consort diagram. Of patients randomized to the device arm (A), randomization failures were largely attributable to device fit or comfort. Of the 36 patients in the device arm who discontinued, the majority of early terminations occurred before a small device option was introduced
Fig. 3
Fig. 3
A Longitudinal analysis of pain scores by visit for all randomized patients (ITT population) and those who completed questionnaires for every study day (PP population). Patients recorded their level of comfort/pain using a six point categorical scale (0 = feels normal to 5 = marked discomfort and inability to swallow solids or liquids necessitating supplemental nutrition). Pain was rated in binary fashion, none (0) vs. any (> 0). Patients completed an Oral Mucositis Symptom Assessment (Supplemental Table 1) from day 1 to day 14 of their first two cycles of chemotherapy. B Analgesic use patients recorded the need for mouth symptom palliation by analgesic medications for days 1-14 of their first two cycles of chemotherapy.  Analgesic use was evaluated in binary fashion.  This figure compares the percent of patients in each arm (CMP device users vs. controls) who did not require analgesics (responders) to control mouth pain during cycle days
See this image and copyright information in PMC

References

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