Proteolytic enzymes are comprised of papain (100 mg), trypsin (40 mg), and chymotrypsin (40 mg). Proteolytic enzymes break down proteins throughout the body for various metabolic processes and can act as anti-inflammatory agents. This product has been evaluated as an intervention for mucositis and radiodermatitis in patients with cancer.
Effectiveness Not Established
Bolderston, A., Lloyd, N.S., Wong, R.K.S., Holden, L., Robb-Blenderman, L., & Supportive Care Guidelines Group. (2005). The prevention and management of acute skin reactions related to radiation therapy: A clinical practice guideline (Practice Guidelines Report #13-7). Toronto, Canada: Cancer Care Ontario. Retrieved from https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=34406.
Purpose & Patient Population:
To develop practice guidelines answering two questions:
- What are the optimal methods to prevent acute skin reactions related to radiation therapy (RT) within the first six months of irradiation?
- What are the optimal methods to manage acute skin reactions related to RT?
Type of Resource/Evidence-Based Process:
Databases searched were PreMEDLINE, MEDLINE, CANCERLIT, and Cochrane Library between January 1980 and April 2004. The name of the initiative was the Cancer Care Ontario’s Program in Evidence-Based Care. The method used was the practice guidelines development cycle. Articles were included based on rigorous inclusion criteria (meta-analysis, systematic reviews, evidence-based practice guidelines, comparative studies, prospectively collected data in at least one trial arm, studies with reported outcomes—degree of skin reaction [using a validated skin reaction tool] and other outcomes reported and articles available as published articles or abstract reports). Exclusion criteria were also identified.
The systematic review included interprofessional members from the Supportive Care Guidelines Group of Cancer Care Ontario and the Program in Evidence-Based Care, an internationally recognized program at McMaster University, Hamilton, Ontario, Canada.
No conflict of interest was identified.
A systematic review of 28 clinical trials was included in analyses; 23 pertained to prevention and 5 addressed management of skin reactions. Two practice guides were reviewed: Oncology Nursing Society and British Columbia Cancer Agency (expert opinion and consensus).
Results Provided in the Reference:
A table of clinical studies presented study descriptions and outcomes of the trials on prevention and management of skin reactions, pain, and itching.
The largest randomized trial compared calendula versus Biafine and was significant (p = 0.03) in reducing the severity of RT dermatitis.
Guidelines & Recommendations:
- Gentle skin washing with water alone or mild soap (unscented, lanolin-free) and water
- Gentle shampooing of the scalp with mild shampoo if receiving RT to the head
- Encourage personal hygiene habits to avoid psychosocial distress. Limiting personal hygiene practices is not recommended.
- Patients who received breast irradiation may use calendula ointment to decrease the occurrence of a grade 2 or higher skin reaction.
Insufficient evidence existed to support or refute the use of
•Topical agents (corticosteroids, sucralfate cream, Biafine® (Ortho Dermatologics), ascorbic acid, aloe vera, chamomile cream, almond ointment, or polymer adhesive skin sealant)
•Oral agents (enzymes, sucralfate)
•Intravenous agents (amifostine)
Gentle skin and hair washing should be unrestricted in patients receiving RT. No barrier exists to using mild soap.
No trials answered the question on management.
- Outcome assessment tools are required, including quality of life tools.
- Trials to assess oral enzymes are needed to confirm studies showing potential for prevention benefit.
- Randomized trials are needed (double-blinded, randomized, controlled trials) about the benefits of moisturizing cream as a preventive measure.
- Randomized trials are needed that address moist desquamation management with the use of dressings as an intervention.
- Trials are needed that explore sites with different risk factors and possible differing management.
Opinions of This Group:
- Use plain, unscented, lanolin-free hydrophilic cream, but discontinue with skin breakdown.
- Low-dose corticosteroid cream may be helpful with itching and irritation, but caution patients about overuse. More evidence is required to make firm recommendations.
Research Evidence Summaries
Gujral, M. S., Patnaik, P. M., Kaul, R., Parikh, H. K., Conradt, C., Tamhankar, C. P., & Daftary, G. V. (2001). Efficacy of hydrolytic enzymes in preventing radiation therapy-induced side effects in patients with head and neck cancers. Cancer Chemotherapy and Pharmacology, 47, S23–S28.
To determine the effect of oral proteolytic enzymes for prevention of acute side effects in patients with head and neck cancer.
Intervention Characteristics/Basic Study Process:
Patients were randomly assigned to the control or experimental group.
The enzymes taken were a combination of papain 100 mg, trypsin 40 mg, and chymotrypsin 40 mg (MUCOS Pharma). Patients took three tablets, three times per day, three days prior to start of radiation therapy (RT), and up to five days after completion.
Mucositis, skin reaction, and dysphagia were graded at each visit during and after RT. Scoring was done at baseline, weekly, and five to six months following treatment.
- The sample was comprised of 98 men.
- Age ranged from 18 to 65 years.
- Patients had T3/T4 cancers of the head and neck region with squamous cell.
- Patients received Cobalt 60 gamma radiation at a standard daily dose of 2 Gy in 25 to 35 fractions over six to seven weeks.
- Thirty-three patients were hospitalized to ensure compliance.
- Indore and Cuttack, India
The study was a prospective, randomized, open-label trial.
- Radiation Therapy Oncology Group (RTOG) criteria
- Compliance was monitored by counting pills.
- Grading was performed by the same person every time.
- Wilcoxon summed was used to test for differences.
- The average skin reaction score was lower in those treated with sucralfate (p < 0.0001).
- The maximal extent of acute toxicity was lower in those who took sucralfate.
- Two patients in the experimental group were dropped due to the most severe acute reactions.
Oral sucralfate may be helpful in reducing the severity of radiodermatitis.
- Slightly more than one-third of the patients had to be hospitalized to ensure compliance with treatment, which suggests the impracticality for clinical use in this population.
- Multiple patients had treatment delays, most of which were associated with social issues.
- Skin reactions per RT dose levels were not compared.