Elliott, E. A., Wright, J. R., Swann, R. S., Nguyen-Tân, F., Takita, C., Bucci, M. K., . . . Radiation Therapy Oncology Group Trial 99-13. (2006). Phase III trial of an emulsion containing trolamine for the prevention of radiation dermatitis in patients with advanced squamous cell carcinoma of the head and neck: results of Radiation Therapy Oncology Group Trial 99-13. Journal of Clinical Oncology, 24, 2092–2097.

This phase 3 trial was designed to compare an emulsion containing trolamine against usual supportive care within each participating institution.

Patients were randomly assigned to one of three treatment arms:  (a) prophylactic trolamine emulsion, (b) interventional trolamine emulsion, and (c) declared institutional preference.

In both trolamine arms, trolamine was applied at four-hour intervals. Patients were instructed to maintain at least four hours between trolamine and radiation therapy (RT).

Trolamine use was discontinued immediately if an allergic reaction occurred or if grade 3 dermatitis was reported in any area larger than 1.5 cm of confluent desquamation or bleeding in the treatment area.

• The sample was comprised of 547 patients (79% male).
• Mean age was 59 years.
• Patients had head and neck cancer.
• Approximately 80% of the patients received an RT dose greater than 60 Gy.
• Of the patients, 53% on study received combined-modality treatment.

Fifty-one institutions in various states in the United States

The study was a randomized, controlled trial.

• The primary outcome was the reduction in grade 2 or higher skin toxicity, per National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 2 and the ONS toxicity scoring tool.
• Secondary outcomes included patient-reported quality of life (QOL).
• Skin assessments and QOL forms were completed before RT, weekly during RT, and weekly for four weeks after RT.
• The Spitzer QOL Index (SQOLI) and the Head and Neck Radiotherapy Questionnaire (HNRQ) were used to measure QOL. A higher score indicated greater toxicity and poorer QOL.

• The rates of grade 2 or higher radiodermatitis were 79%, 77%, and 79% in the prophylactic, interventional, and institutional preference arms, respectively.
• Rates of grade 3 or 4 dermatitis did not differ, with rates of 25%, 25%, and 23% in the three arms, respectively.
• Confluent moist desquamation was observed in 7%, 10%, and 8% of patients in the prophylactic, interventional, and institutional preference arms, respectively.
• Ulceration, hemorrhage, and necrosis were experienced in 2%, 3%, and 1% of the patients in the three arms, respectively.
• The ONS toxicity score reported a small to moderate amount of moist desquamation in 31%, 28%, and 34% of patients in the prophylactic, interventional, and institutional preference arms, respectively.
• No significant differences were found in QOL.
• Fourteen products were reported as standard of care. The most commonly used product was Aquaphor, which was the institutional preference for 39% of the patients.
• A slightly higher rate of treatment breaks was reported in the institutional arm than in both trolamine arms for current and former smokers, but the breaks on average were shorter.

The results demonstrate no advantage for the use of trolamine in reducing the incidence of grade 2 or higher radiodermatitis or improving patient-reported QOL.

• Absence of patient diaries to record compliance with application directions, the timing and number of applications, and the full amount of product used was a limitation. The product log for this trial was a record of the number of tubes supplied to each participant.
• The study was not blinded or placebo-controlled, which introduced the possibility that the skin grading and QOL assessments were subject to reviewer and patient bias.