Koukourakis, G.V., Kelekis, N., Kouvaris, J., Beli, I.K., & Kouloulias, V.E. (2010). Therapeutics interventions with anti-inflammatory creams in post radiation acute skin reactions: A systematic review of most important clinical trials. Recent Patents on Inflammation & Allergy Drug Discovery, 4(2), 149–158.

To investigate through a systematic review what topical treatments are currently advocated to manage acute skin reactions, including creams, ointments, and dressings, and what evidence there is to support the use of these treatments

Databases used were  MEDLINE and Cochrane Central Register of Controlled Trials. Keywords searched radiation therapy, epidermis, acute skin reactions, and therapy. Studies were included if they

• Were written in the English language
• Were controlled trials
• Provided information about the post-radiation acute skin reactions
• Had patients who were eligible for treatment.

No exclusion criteria were identified in the article.

Total references retrieved, evaluation method, and comments on the literature used were not reported.
 

• The final number of studies included in the review was 17, 15 studies in which an agent was used and 2 studies with washing only.
• The total sample size across studies was 1,968 participants, with a range of 10–194 participants in one arm and 39–366 participants in an entire study.
• Radiation sites included breast, head and neck, pelvic, chest, and abdomen.

Patients were undergoing active treatment.

• Washing: Significant decrease in itching, erythema, and desquamation was found in the group that washed with soap and water. A higher incidence of moist desquamation was found in the no washing group (33%) as compared to the washing with soap and water group (14%). 
• Aloe vera: One study showed a benefit at higher cumulative doses. Another showed no difference in maximum severity or time to onset of grade 2 radiodermatitis. Still another showed a detriment in that dry desquamation was higher in the aloe vera arm (70%) as compared to topical aqueous cream (41%). 
• Biafine (trolamine): Two studies showed no significant decrease in skin reaction when comparing no treatment, Aquaphor, Lipiderm, and Biafine. A third study showed a decrease in grade 2 or greater skin reaction, pain, and treatment interruptions. 
• Hyaluronic acid: Two studies showed a significant benefit (i.e., decreased severity and delayed onset of radiodermatitis) among patients receiving hyaluronic acid as compared to a placebo or unidentified control. 
• Corticosteroids: Of two randomized, double-blinded studies using corticosteroid cream as a prophylaxis, the study by Bostrom et al. found a 25% compared to 60% incidence of grade IV radiation dermatitis (corticosteroid vs. emollient). The second study did not find significant results in favor of corticosteroid. Another study showed no significant difference between a corticosteroid cream and a placebo. Still another study showed a significant difference between a corticosteroid cream and clobetasone, but most of the patients in both arms experienced moderate-to-maximum skin reactions. 
• Sulcrafate: A randomized study in head and neck cancer found no difference in erythema, but found a higher incidence of moist desquamation in the topical sulcrafate prophylaxis group. A large (N = 357) randomized study in head and neck (n = 107), breast (n = 229), and anorectal (n = 30) cancer by found no significant difference among the topical sulcrafate, topical aqueous cream, and no cream groups. Another study (N = 44) found a significant reduction in grade 2 radiodermatitis and more rapid healing in the topical sulcrafate group among patients with breast cancer. A different study (N = 39) compared topical sorbolene and sorbolene plus sulcrafate to manage grade 3 or greater skin toxicity and found no differences between the two groups. Another study showed no benefit of using oral sulcrafate as a prophylactic agent for late reaction in prostate cancer. A final study showed no benefit of using oral sulcrafate as a prophylactic agent in preventing skin reactions in head and neck cancer. 
• Barrier film: A study compared No-Sting barrier film to topical sorbolene as prophylaxis for moist desquamation among patients with breast cancer, showed a significant benefit. Another study  (N = 50 ) examined the use of Dermofilm in reducing pain and irritation. “Favorable” results were reported, but a larger study was recommended.
• Anti-microbials: No study results were found. The authors cautioned against using antimicrobials as a prophylactic agent related to our knowledge of drug resistance. 
• Dressings: One study examined healing after radiation treatment among 18 patients and found the mean healing time was 13 days. There was no comparison arm. Another study compared the use of sliver leaf nylon dressings applied to the perineum of 15 patients with anal or gynecologic cancers to historic controls. Patients who received the silver leaf nylon dressings had significantly reduced incidence of grade 3 and 4 reactions. A different study (N = 60) showed a higher incidence of radiodermatitis in the sulcrafate arm among patients with head and neck cancer.  Another study (N = 44) showed a significant benefit to breast cancer patients. One very small study (N = 15) showed a benefit of using sliver leaf nylon dressings to reduce grade 3 and 4 radiodermatitis of the perineum among anal and gynecologic cancers.

Washing with soap and water consistently demonstrated a benefit. The evidence for the use of aloe vera is mixed with one study showing harm. Biafine did not demonstrate a benefit nor a harm. Hyaluronic acid showed a benefit. Corticosteroid showed mixed results, with one study showing favorable results, two showing no increased benefit, and one study showing mixed results. Most of the evidence on topical sulcrafate shows no increased benefit in preventing and managing radiodermatitis. Dermofilm, a barrier film, showed a significant benefit in reducing moist desquamation among patients with breast cancer in one small study.

Additional studies with a larger sample and a blinded randomized controlled design are needed.