PEP Topic 

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

Guideline/Expert Opinion

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:

  1. What are the optimal methods to prevent acute skin reactions related to radiation therapy (RT) within the first six months of irradiation?
  2. 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.

Nursing Implications:

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.

Future Research:

  • 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.

Wong, R.K., Bensadoun, R.J., Boers-Doets, C.B., Bryce, J., Chan, A., Epstein, J.B., . . . Lacouture, M.E. (2013). Clinical practice guidelines for the prevention and treatment of acute and late radiation reactions from the MASCC Skin Toxicity Study Group. Supportive Care in Cancer, 21, 2933–2948. 

PROFESSIONAL GROUP: Multinational Association for Supportive Care in Cancer (MASCC) Skin Toxicity Study Group

doi: 10.1007/s00520-013-1896-2

Purpose & Patient Population:

PURPOSE: To develop evidence-based guidelines to prevent and treat skin toxicity (acute and late) from radiation therapy. Use of these guidelines was intended for practitioners who encounter patients with skin changes associated with radiation therapy.
TYPES OF PATIENTS ADDRESSED: Patients who have received or will receive radiation therapy

Type of Resource/Evidence-Based Process:

RESOURCE TYPE: Evidence-based guideline
PROCESS OF DEVELOPMENT: The Skin Toxicity Study Group is one of 17 study groups of the Multinational Association for Supportive Care in Cancer (MASCC). The first original search was from 1980–2004 and was used by the Cancer Care Ontario guideline group. This search was updated in 2010 for a book chapter on radiation dermatitis, including the original search strategy from 1980–2004 in addition to a search without language restriction for 2004–August 2010. For the MASCC guideline, a second update from 2010–April 2011 was conducted for the meeting. A final update was completed in July 2012 prior to publication of the manuscript.

DATABASES USED: MEDLINE for initial and subsequent updates; PreMEDLINE, Cochrane Library, and CANCERLIT for the original search 1980–2004; Embase for 2010–2012; and conference proceedings of the American Society of Clinical Oncology for 2004–2012. National Guidelines Clearinghouse was used for existing practice guidelines.

KEYWORDS: Radiation dermatitis for acute reactions; telangiectasia and cutaneous fibrosis for late reactions

INCLUSION CRITERIA: Randomized controlled trials, guideline papers, meta-analyses, and systematic reviews. Studies that included any control group met the definition of a controlled study. Inclusion required that grade of skin reaction was evaluated as an outcome with primary interest greater or equal to moist desquamation. Pain, itching, and quality of life also were included if available. For late reaction dermatitis, trials using prospective designs were used.

EXCLUSION CRITERIA: Unpublished articles

Phase of Care and Clinical Applications:

PHASE OF CARE: Multiple phases of care

Results Provided in the Reference:

Acute radiation dermatitis recommendations were based on guidelines consisting of four general systematic reviews, two for specific topics, two evidence-based guidelines, and one consensus guideline. There were 56 randomized controlled trials–45 prevention, 9 treatment, and 1 combined prevention and treatment. Late radiation effect recommendations were based on one RCT; one prospective, observational study; and two prospective, single-arm studies.

Guidelines & Recommendations:

Strong recommendation:
  • Gentle washing with water (mild soap or shampoo optional)
  • Antiperspirants during breast radiation therapy
  • Prophylactic topical steroids (mometasone) for risk reduction of discomfort and itching
Weak recommendation:
  • Prophylactic silver sulfadiazine cream in patients with breast cancer to reduce radiation dermatitis score
Strong recommendation against:
  • Prophylactic aloe vera or trolamine
No recommendation possible:
  • Prophylactic topical sulcrate/derivatives, hyaluronic acid, ascorbic acid, silver leaf dressing, LED, Theta-Cream, dexpanthenol, and calendula
  • Oral proteolytic enzymes, sucralfate, zinc, and pentoxifylline in standard clinical practice
Established radiation-induced telangiectasia and fibrosis:
  • Weak recommendation for pulse dye laser for visual appearance
  • Weak recommendation against pentoxifylline for reduction of fibrosis in standard clinical practice
Patient education materials:
  • Validation prior to use
  • Sixth grade reading level and tables preferred
  • Specific products to purchase with examples
  • Behaviors to avoid
  • Contact information for physician and when to call for symptom management

Nursing Implications:

Nurses need to keep updated on current studies and guidelines related to care of patients receiving radiation therapy as well as potential acute and long-term effects to the skin. Nurses are in a unique position to educate staff and patients on evidenced-based skin care. Potential skin care practices for patients undergoing radiation need to be evaluated through well-designed research studies.

Systematic Review/Meta-Analysis

Chan, R.J., Webster, J., Chung, B., Marquart, L., Ahmed, M., & Garantziotis, S. (2014). Prevention and treatment of acute radiation-induced skin reactions: A systematic review and meta-analysis of randomized controlled trials. BMC Cancer, 14, 53-2407-14-53.

doi: 10.1186/1471-2407-14-53


STUDY PURPOSE: To assess the effects of interventions aiming to prevent or manage radiation-induced skin reactions (RISRs) in people with cancer
TYPE OF STUDY: Meta-analysis and systematic review

Search Strategy:

DATABASES USED: Cochrane Skin Group Specialized Register, CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL, and LILACS
KEYWORDS: Radiation-induced skin reactions; radiation dermatitis; systemic review; meta-analysis; randomized, controlled trials (RCTs)
INCLUSION CRITERIA:  All patients receiving external beam radiation; RCTs

Literature Evaluated:


EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Risk of bias was assessed according to the Cochrane handbook

Sample Characteristics:

FINAL NUMBER STUDIES INCLUDED =  47 studies were included in qualitative synthesis (six quantitative syntheses)
KEY SAMPLE CHARACTERISTICS: Receiving external beam radiation

Phase of Care and Clinical Applications:

PHASE OF CARE: Active antitumor treatment 


Forty-seven studies on the six types of interventions for managing RISR were reviewed (oral systemic medications, skin care practice [washing and deodorant], steroidal topical ointment/cream, dressings, nonsteroidal cream/ointment, and LED vs sham treatment). The results of a meta-analysis of Wobe Mugos versus a control showed an odds ratio of 0.13 (p < 0.0004) in favor of Wobe Mugos. There was a mean difference of -09/92 (p < 0.0001) for Wobe Mugos treatment across two studies including 219 patients. Pentoxifylline was not shown to have an effect. Oral sucralfate and oral antioxidants did not show an effect. Various topical steroids showed mixed results. A meta-analysis of trolamine showed no significant benefit. Washing the skin and using deodorants did not affect skin toxicity scores. Evidence was restricted because of the variation of interventions as it was not easily detectable which products would be most effective. There was no strong evidence for any of the products included in the study. The study quality of most of the included RCTs was only fair, and there were few interventions that were examined in multiple studies.


Additional research studies establishing the effectiveness of multiple skin care products is needed. The findings of this meta-analysis in regard to Wobe Mugos were positive, suggesting that additional, well designed research is warranted.


  • Small number of studies per interventions for a meta-analysis
  • Variation in products used
  • No clear information on anatomical sites where the products were used

Nursing Implications:

Additional research on skin care products used to manage RISR is needed.

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.


Study Purpose:

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.

Sample Characteristics:

  • 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.


  • Multisite
  • Indore and Cuttack, India

Study Design:

The study was a prospective, randomized, open-label trial.

Measurement Instruments/Methods:

  • 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 enzymes (p < 0.0001).
  • The maximal extent of acute toxicity was lower in those who took enzymes.
  • Two patients in the experimental group were dropped due to the most severe acute reactions.


Oral proteolytic enzymes 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.