Efficacy of a novel device for cryoprevention of oral mucositis: a randomized, blinded, multicenter, parallel group, phase 3 trial

Abstract

Cryoprevention (CP) using ice (IC) is an effective strategy to prevent chemotherapy-induced oral mucositis (OM). However, the use of IC may cause adverse reactions and requires water of safe quality to minimize risk of serious infections. This randomized, blinded, parallel group, phase 3 trial was conducted in five Scandinavian centers. Eligible patients were diagnosed with multiple myeloma or lymphoma, scheduled to receive conditioning with high-dose chemotherapy prior to autologous hematopoietic stem cell transplantation (ASCT). Patients were assigned to cooling with IC or a novel intraoral cooling device (ICD). The primary outcome was the highest OM score during the study period, expressed as peak value on the Oral Mucositis Assessment Scale (OMAS–total). When the entire study population (n = 172) was analyzed for peak OMAS–total, the two cooling methods were equally effective. However, when the lymphoma group was analyzed separately, the ICD significantly reduced the peak OMAS–total score to a greater extent compared to IC (x̄ ± SD; 1.77 ± 1.59 vs. 3.08 ± 1.50; p = 0.047). Combined with existing evidence, the results of the present trial confirm that CP is an effective method to prevent OM. ClinicalTrials.gov. NCT03203733.

Cryopreventive temperatures prior to chemotherapy

“…Further, the ICD proved to enhance the e cacy of conventional IC in prevention of OM in patients with lymphoma, whereas e cacy results were comparable between the two cooling methods in the myeloma group. The collective tolerability data were in accordance with the previous study in healthy volunteers [19]. It was also shown that cooling with the ICD 15°C was better tolerated than the ICD 8°C but displayed inferior capacity in temperature reduction [28].…”

“…Until recently, when a novel intraoral cooling device (ICD) was introduced, only modest resources had been devoted to further develop the modality of cooling in conjunction with chemotherapy. This is somewhat surprising since the superiority of OC for prevention of chemotherapy-induced oral mucositis (OM) has been demonstrated in several trials [16,19,26,27]. Cooling with the ICD was equally effective but better tolerated when compared to ice chips (IC) in healthy volunteers [18].…”

“…The ICD is made up of a closed conduit system with continuously circulating water; and can be set to operate at different temperatures. In a randomized controlled trial, the ICD set to 8°C was compared to IC, con rming the e cacy of OC for prevention of OM [19]. However, the ICD was better tolerated and showed superiority to IC in the subgroup with lymphoma patients.…”

Moderate temperature reduction is sufficient for prevention of 5-fluorouracil-induced oral mucositis: an experimental in vivo study in rats

“…Combined with existing evidence, the results of the present study confirm that CT is an effective strategy to prevent the events which may precede clinically established OM. Furthermore, suggesting that cooling at higher temperatures, e.g., using cooling devices that can operate at higher temperatures [ 12 , 14 ], may be advantageous in clinical settings to prevent chemotherapy-induced OM.…”

“…In particular, this pertains to early events that precede clinically established OM. Cryotherapy (CT), i.e., the use of ice or cooling devices to cool the oral mucosa, continues to have considerable promise in clinical settings to reduce chemotherapy-induced OM [8][9][10][11][12]. However, while CT effectively alleviates OM in patients receiving chemotherapy, the knowledge is scarce regarding the ideal temperature for prevention of OM.…”