Chan, R.J., Mann, J., Tripcony, L., Keller, J., Cheuk, R., Blades, R., . . . Walsh, C. (2014). Natural oil-based emulsion containing allantoin versus aqueous cream for managing radiation-induced skin reactions in patients with cancer: A phase 3, double-blind, randomized, controlled trial. International Journal of Radiation Oncology, Biology, Physics, 90, 756–764.

To investigate the effects of a natural, oil-based emulsion containing allantoin versus aqueous cream for preventing and managing radiation-induced skin reactions

Patients received either cream 1 (the natural, oil-based emulsion containing allantoin [Moogoo Udder Cream]) or cream 2 (aqueous cream). The allantoin emulsion contained multiple other ingredients, including aloe. Patients were stratified by irradiated site, body mass index, and smoking status, and they randomly were assigned to the intervention. Patients applied the cream to irradiated skin twice daily or more as needed. If moist desquamation occurred, the treatment was discontinued until healing occurred. Study assessments were completed weekly. The creams for both arms had a similar appearance and were manufactured in a plain tube. The participants and researchers remained blinded until the end of the study when codes on the tubes revealed the study arm. Inter-rater reliability was measured and resulted in an intraclass correlation of 1.0 (perfect agreement). A sample size calculation was conducted; 81 participants were required for each arm, and ≥ 81 participants completed each arm.

• N = 173 (randomized)
• MEAN AGE = 60–61 years
• MALES: 64.4%, FEMALES: 35.6%
• KEY DISEASE CHARACTERISTICS: Lung, breast, and head and neck cancers

• SITE: Single-site
• SETTING TYPE: Outpatient
• LOCATION: Brisbane, Australia

• PHASE OF CARE: Active antitumor treatment

Double-blinded, blocked, randomly assigned, controlled, phase III clinical trial

• National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE v4) to measure skin toxicity
• Skindex-16 to measure skin-related quality of life
• Brief Pain Inventory (BPI) to measure pain
• Itching was measured using a numeric analog scale (NAS) where 0 = none and 10 = worst imaginable.

Patients who received cream 1 had a significantly lower average CTCAE score at week 3 (p < 0.05) but had statistically higher average levels of skin toxicity at weeks 7, 8, and 9 (all p < 0.001). Similar results were observed when skin toxicity was analyzed by grades. In regard to pain, patients in the cream 2 group had significantly higher average worst-pain scores (p < 0.05) and itching (p = 0.046) compared to the cream 1 group at week 3; however, these differences were not observed during other weeks. In addition, there was a strong trend for cream 2 to reduce the incidence of grade 2 or more skin toxicity in comparison with cream 1 (p = 0.056). Overall, more participants in the cream 1 group were required to use another topical treatment at weeks 8 (p = 0.049) and 9 (p = 0.01).

Overall, this was a well designed study. However, some participants used prescribed creams in addition to the assigned study cream, making it difficult to know the true effects of the study creams. The cream containing allantoin performed better during the first five weeks of treatment but worse thereafter.

• Unintended interventions or applicable interventions not described that would influence results
• Questionable protocol fidelity
• Other limitations/explanation: This study was partially funded by an industry (Moogoo Skin Care in Australia). However, the authors report that the industry was not involved in the study design or the preparation of the manuscript. The participants were told to apply the cream twice per day or as needed. Participants in both arms admitted to using additional creams other than the assigned study cream. For example, 34 of 89 participants (38%) in the cream 1 (the study cream with allantoin) arm reported using an additional cream at week 8. Limitations included the study's inability to measure skin dose. Instructing patients to apply as needed contributes to this limitation.

Additional studies with improved “buy-in” from participant healthcare providers to reduce the use of non-study creams are needed. This study does not provide strong evidence for the effectiveness of this intervention as findings varied at different time points and there were several study limitations. Nurses' awareness of the importance of using the CTCAE for grading skin toxicities related to topical treatments is vital in standardizing assessments. Moogoo Udder Cream is available in the United States (http://moogoousa.com/udder-cream-skin-milk.html), but not in stores.