Treister, N., Nieder, M., Baggott, C., Olson, E., Chen, L., Dang, H., . . . Sung, L. (2016). Caphosol for prevention of oral mucositis in pediatric myeloablative haematopoietic cell transplantation. British Journal of Cancer, 116, 21–27.

DOI Link

Study Purpose

To determine whether topically administered Caphosol, rinsed orally four times daily at the initiation of conditioning, reduces the duration of severe oral mucositis (OM) compared with placebo among children and adolescents undergoing hematopoietic cell transplantation (HCT)

Intervention Characteristics/Basic Study Process

Supplied Caphosol A (phosphate solution) and B (calcium solution) or sterile 0.9% sodium chloride solution were provided by two unblinded pharmacists after patients were randomized 1:1 between treatment and control groups. The nurses mixed the Caphosol in the syringes to form a pH-neutral supersaturated solution. The children and adolescents rinsed their mouths thoroughly for one minute, gargled, and spit with one-half of the mixed solution. They repeated with the remaining solution for a total rinse time of two minutes. Younger children with small mouths could rinse with a reduced volume. Participants rinsed four times per day (two rinses per episode) at approximately evenly spaced intervals. The therapy was initiated on the first day of conditioning and continued daily until after day 20 or hospital discharge, whichever occurred first. The subjects were assessed daily for OM by trained study staff until refusal by patient to participation, day +2-, or discharge home. Common Terminology Criteria for Adverse Events (CTCAE) criteria were used to assess toxicity.

Sample Characteristics

  • N = 220   
  • MEAN AGE = 13.7 years
  • MALES: 56 placebo, 62 caphosol; FEMALES: 54 placebo, 48 caphosol
  • CURRENT TREATMENT: Chemotherapy, combination radiation and chemotherapy
  • KEY DISEASE CHARACTERISTICS: Scheduled to undergo myeloablative autologous or allogeneic HCT for any indication
  • OTHER KEY SAMPLE CHARACTERISTICS: Patients were aged 4–21 years. Graft sources included bone marrow (BM), umbilical cord blood (UCB), and peripheral blood stem cells (PBSCs). Eligible donors were HLA-matched, mismatched for a single HLA locus of A, B, or C, or DR, BM, PBSCs, or UCB. At least four of six loci matched at A, B, and DR. Patients could not have received palifermin within 30 days and could not have been previously treated with Caphosol. Patients were stratified by type of graft and type of conditioning regimen.

Setting

  • SITE: Multi-site   
  • SETTING TYPE: Inpatient    
  • LOCATION: International

Phase of Care and Clinical Applications

  • PHASE OF CARE: Active antitumor treatment
  • APPLICATIONS: Pediatrics

Study Design

Phase III, international, multicenter, randomized, double-blinded, placebo-controlled, prospective clinical trial. The primary endpoint was the duration of severe OM (World Health Organization [WHO] score of 3 or greater).

Measurement Instruments/Methods

  • WHO Oral Toxicity Scale
  • Mouth Pain Categorical Rating Scale
  • Modified Oral Mucositis Daily Questionnaire
  • Opoid analgesic use
  • Total parenteral nutrition use
  • Fever and neutropenia incidence
  • Invasive bacterial infections

Results

The mean duration of severe OM was not reduced among Caphosol (4.5, SD = 5 days) versus placebo (4.5, SD = 4.8; p = 0.99) recipients. No significant differences existed in any of the secondary endpoints between the groups.

Conclusions

Caphosol did not reduce severe OM compared with placebo among children and adolescents undergoing myeloablative HCT.

Limitations

  • Missing data
  • Supportive care was not standardized.
  • Pretransplantation dental evaluation or ongoing oral care was not collected.
  • The study was underpowered.
  • The WHO toxicity scale does not identify reasons children do not eat or drink that are unrelated to mouth pain.

Nursing Implications

Caphosol did not reduce severe OM compared with placebo among children and adolescents undergoing myeloablative HCT. Effective interventions for OM is needed in this and in other populations.