The Impact of Oral Cryotherapy and Chewing Gum Interventions

Overview

Chemotherapy-induced nausea and vomiting (CINV) and taste alterations continue to be among the most common and most severe side effects that women receiving adjuvant chemotherapy for breast cancer suffer. Despite standard antiemetic treatments, a significant proportion of patients experience inadequate symptom management, necessitating investigation into complementary non-pharmacological interventions such as oral cryotherapy and chewing gum in women undergoing Adriamycin-Cyclophosphamide therapy. 135 female patients recently diagnosed with early-stage breast cancer participated in a single-center, three-arm randomized controlled trial. Random assignment was used to assign participants to the oral cryotherapy group (OCG), chewing gum group (CGG), or control group (CG). Interventions were used during the initial cycle of chemotherapy.

Chemotherapy-induced nausea and vomiting (CINV) remains one of the most distressing and prevalent side effects of cancer treatment, affecting a substantial proportion of patients undergoing chemotherapy. Despite advances in antiemetic regimens, CINV continues to occur in many patients, significantly impairing their quality of life and clinical outcomes. The onset and severity of CINV are largely influenced by the emetogenic potential of chemotherapeutic agents, with drugs such as cyclophosphamide and doxorubicin frequently triggering acute symptoms within the first 1-5 days post-administration. CINV is a multifactorial process involving both peripheral and central pathways. Cytotoxic agents stimulate the release of serotonin from enterochromaffin cells in the gastrointestinal tract, which subsequently activates 5-hydroxytryptamine 3 (5-HT₃) receptors in the chemoreceptor trigger zone (CTZ) of the central nervous system, leading to emesis. The CTZ, located in the area postrema of the medulla oblongata, is particularly vulnerable due to its lack of a complete blood-brain barrier, facilitating the access of circulating emetogenic substances. Beyond the immediate physical discomfort, poorly managed CINV contributes to complications including malnutrition, dehydration, electrolyte imbalances, metabolic disturbances, increased infection risk, and significant psychological distress. These complications often necessitate additional medical interventions and hospitalizations, increasing the financial and emotional burden on patients, caregivers, and healthcare systems. Despite routine pharmacologic interventions, many patients continue to experience CINV, which points to the importance of effective, accessible, and patient-centered non-pharmacologic approaches. Oral cryotherapy, localized cooling of the oral mucosa via ice application, has gained attention as a low-cost, well-tolerated method primarily used to prevent chemotherapy-induced oral mucositis. This method induces vasoconstriction of oral blood vessels during intravenous chemotherapy infusion, thereby limiting drug delivery to oral tissues. Although cryotherapy has been explored in other contexts, such as surgical nausea and gynecological care, its potential for CINV management remains underinvestigated. Another promising non-pharmacologic intervention is chewing gum, which stimulates salivary flow and may help mitigate the oral side effects of chemotherapy. Saliva has intrinsic protective and antimicrobial properties, and its production may be reduced by chemotherapy-induced cytotoxicity on salivary glands.