The incidence of grade 1 to 2 skin toxicity declined by almost 50% in women who used the melatonin compound versus those who used a placebo emulsion. Conversely, four times as many patients had grade 0 toxicity with melatonin versus placebo, as reported at the American Society of Clinical Oncology's 2010 Breast Cancer Symposium.
Women older than 50 and smokers derived particular benefit from the melatonin emulsion, said Merav A. Ben-David, MD, of Sheba Medical Center in Ramat-Gan, Israel.
"What we discovered was that, with a follow-up of two weeks after radiation therapy, women who used the melatonin cream had less acute skin toxicity," Ben-David told MedPage Today.
As many as 90% of breast cancer patients have acute skin reactions during radiation therapy, reaching grade 2 severity in about a third of cases. Melatonin-containing topical compounds have shown radioprotective effects in preclinical models, said Ben-David. Additionally, in vitro studies have shown that melatonin reduces oxidative damage to human skin fibroblasts.
Extending investigation of topical melatonin to the clinical setting, Ben-David and colleagues enrolled 47 breast cancer patients scheduled for adjuvant radiation therapy following lumpectomy. Patients were randomized to the melatonin emulsion or to an identical cream without melatonin.
The patients had a mean age of 54, three-fourths had fair-complexioned skin, and a fourth were smokers. The two treatment groups did not differ significantly with respect to any baseline characteristics evaluated.
Following lumpectomy, all patients received a total radiation dose of 50 Gy, administered to the entire breast in 2-Gy fractions. Patients applied randomized therapy twice daily throughout the radiation treatment. Skin toxicity was assessed by Radiation Therapy Oncology Group (RTOG) criteria two weeks after completion of radiation therapy.
Ben-David said that 22 patients in the melatonin group and 19 in the placebo group finished the study and had complete data.
At the end of the study, nine (41%) patients in the melatonin group had RTOG grade 0 skin toxicity and 13 (59%) had RTOG grade 1 to 2 toxicity. In contrast, two (11%) patients in the placebo group had an RTOG score of 0, and 17 (89%) had RTOG scores of 1 to 2 (P=0.038).
Subgroup analyses identified two groups of patients who appeared to derive greater benefit from the topical melatonin preparation. Among patients ages 50 and younger, five of 13 (39%) in the melatonin group had RTOG grade 0 skin toxicity compared with two of seven (29%) in the placebo group, a nonsignificant difference. Among women older than 50, four of nine (44%) in the melatonin group had RTOG grade 0 compared with none in the placebo group (P=0.021).
Analysis by smoking status showed that smokers had a mean RTOG score of 0.6 at the end of the study compared with about 1.7 among nonsmokers (P=0.007).
Ben-David noted that skin toxicity was less severe than what has been reported in the literature, as a total of seven patients (15%) had a maximum score of RTOG grade 2.
Patients in the two groups reported no differences in subjective skin sensation, including stinging, burning, tingling, roughness, dryness, and pain. Three patients exhibited skin allergy to the melatonin cream.
On the basis of the results, the melatonin compound will be evaluated in a larger phase III randomized study, which will have a commercially available skin treatment as the control.
Ben-David and co-investigators reported that they had no relevant disclosures.
Zalman S. Agus, MD Emeritus Professor
University of Pennsylvania School of Medicine