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Use of trolamine to prevent and treat acute radiation dermatitis: a systematic review and meta-analysis

ABSTRACT

Objective:

to evaluate the effects of trolamine in the prevention or treatment of radiation dermatitis.

Method:

systematic review and meta-analysis. Detailed individual search strategies for Cinahl, Cochrane Library Central, LILACS, PubMed, and Web of Science were developed in January 2016. A manual search was also performed to find additional references. A grey literature search was executed by using Google Scholar. Two researchers independently read the titles and abstracts from every cross-reference. The risk of bias of the included studies was analyzed by the Cochrane Collaboration Risk of Bias Tool. The quality of evidence and grading of strength of recommendations was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE).

Results:

seven controlled clinical trials were identified. The controls used were calendula, placebo, institutional preference / usual care, Aquaphor®, RadiaCare™, and Lipiderm™. The studies were pooled using frequency of events and risk ratio with 95% confidence intervals, in subgroups according to radiation dermatitis graduation.

Conclusion:

based on the studies included in this review, trolamine cannot be considered as a standardized product to prevent or treat radiation dermatitis in patients with breast and head and neck cancer.

Descriptors:
Review; Radiodermatitis; Skin Care; Radiotherapy; Nursing

RESUMO

Objetivo:

avaliar os efeitos da trolamina na prevenção ou no tratamento da radiodermatite.

Método:

revisão sistemática e meta-análise. Em janeiro de 2016, foram desenvolvidas estratégias detalhadas de busca individual para Cinahl, Cochrane Library Central, LILACS, PubMed e Web of Science. Também foram realizadas buscas manuais para encontrar referências adicionais. Se utilizou Google Scholar para buscar a literatura cinzenta. Dois investigadores leram os títulos e resumos de cada referência cruzada de forma independente. O risco de viés dos estudos incluídos foi analisado com a ferramenta Cochrane Collaboration Risk of Bias Tool. A qualidade das evidências e a classificação da força das recomendações foram avaliadas mediante os Grades of Recommendation, Assessment, Development and Evaluation (GRADE).

Resultados:

foram identificados sete ensaios clínicos controlados. Os controles utilizados foram calêndula, placebo, preferência institucional / atenção padrão, Aquaphor®, RadiaCare™ e Lipiderm™. Os estudos foram agrupados utilizando a frequência de eventos e o índice de risco com intervalos de confiança de 95% em subgrupos, de acordo com a graduação da radiodermatite.

Conclusão:

com base nos estudos incluídos nesta revisão, a trolamina não pode ser considerada um produto padronizado para a prevenção ou o tratamento da radiodermatite em pacientes com câncer de mama e cabeça e pescoço.

Descritores:
Revisão; Radiodermatite; Higiene da Pele; Radioterapia; Enfermagem

RESUMEN

Objetivo:

evaluar los efectos de la trolamina en la prevención o el tratamiento de la radiodermatitis.

Método:

revisión sistemática y meta-análisis. En enero de 2016 se desarrollaron estrategias detalladas de búsqueda individual para Cinahl, Cochrane Library Central, LILACS, PubMed y Web of Science. También se realizaron búsquedas manuales para encontrar referencias adicionales. Se utilizó Google Scholar para buscar literatura gris. Dos investigadores leyeron los títulos y los resúmenes de cada referencia cruzada independientemente. El riesgo de sesgo de los estudios incluidos fue analizado por la herramienta Cochrane Collaboration Risk of Bias Tool. La calidad de la evidencia y la clasificación de la fuerza de las recomendaciones se evaluó mediante los Grades of Recommendation, Assessment, Development and Evaluation (GRADE).

Resultados:

se identificaron siete ensayos clínicos controlados. Los controles utilizados fueron caléndula, placebo, preferencia institucional / atención habitual, Aquaphor®, RadiaCare™ y Lipiderm™. Los estudios se agruparon utilizando la frecuencia de eventos y la razón de riesgo con intervalos de confianza del 95%, en subgrupos según la graduación de radiodermatitis.

Conclusión:

con base en los estudios incluidos en esta revisión, la trolamina no puede considerarse un producto estandarizado para prevenir o tratar la radiodermatitis en pacientes con cáncer de mama y cabeza y cuello.

Descriptores:
Revisión; Radiodermatitis; Cuidados de la Piel; Radioterapia; Enfermería

Introduction

The most common effect of radiotherapy is radiation dermatitis, which has greater impact in patients with head and neck and breast cancer11 Cui Z, Xin M, Yin H, Zhang J, Han F. Topical use of olive oil preparation to prevent radiodermatitis: results of a prospective study in nasopharyngeal carcinoma patients. Int J Clin Exp Med. [Internet] 2015 [cited June 14 2016];8(7),11000-6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565279/.
https://www.ncbi.nlm.nih.gov/pmc/article...
. About 80 to 90% of these patients treated by radiotherapy experience radiation dermatitis during treatment22 Häfner MF, Fetzner L, Hassel JC, Debus J, Potthoff K. Prophylaxis of Acute Radiation Dermatitis with an Innovative FDA-Approved Two-Step Skin Care System in a Patient with Head and Neck Cancer Undergoing a Platin-Based Radiochemotherapy: A Case Report and Review of the Literature. Dermatology. 2013;227: 171-4. doi: http://dx.doi.org/10.1159/000353974
http://dx.doi.org/10.1159/000353974...
-33 Fernández-Castro M, Martín-Gil B. Efectiveness of topical therapies in patients with breast cancer that experience radiodermatitis. A systematic review. Enferm Clin. 2015;25(6):327-43. doi: 10.1016/j.enfcli.2015.06.003
https://doi.org/10.1016/j.enfcli.2015.06...
.

The skin is an organ with high radiosensitivity and susceptible to damage by radiotherapy due to rapid cell proliferation and maturation. The epidermis loses a percentage of its basal cell exposure beginning at the first fractionated dose of radiotherapy, and the repeated exposure of the subsequent fractions leads to continuous cell destruction, which avoids tissue repair44 McQuestion M. Evidence-Based Skin Care Management in Radiation Therapy: Clinical Update. Semin Oncol Nurs. 2011;27(2):e1-e17. doi: 10.1016/j.soncn.2011.02.009
https://doi.org/10.1016/j.soncn.2011.02....
.

Although the skin damage starts after the first exposure to radiation, the clinical signs are often present from the second week of radiotherapy. They are characterized by mild erythema, which can develop to dry or moist desquamation, and ulcerations in some cases55 González-Sanchís A, Vicedo-González A, Brualla-González L, Gordo-Partearroyo JC, Iñigo-Valdenebro R, Sánchez-Carazo J, et al. Looking for complementary alternatives to CTCAE for skin toxicity in radiotherapy: quantitative determinations. Clin Transl Oncol. 2014;16(10):892-7. doi: 10.1007/s12094-014-1163-0
https://doi.org/10.1007/s12094-014-1163-...
-66 O’Donovan A, Coleman M, Harris R, Herst P. Prophylaxis and management of acute radiation-induced skin toxicity: a survey of practice across Europe and the USA. Eur J Cancer Care (Engl). 2015;24(3):425-35. doi: 10.1111/ecc.12213
https://doi.org/10.1111/ecc.12213...
.

Acute skin reactions generate local discomfort, itching and varied degrees of pain that impact the quality of life of patients and affect the therapeutic efficacy and the planning of radiotherapy, considering that severe intensity lesions can cause interruption of treatment11 Cui Z, Xin M, Yin H, Zhang J, Han F. Topical use of olive oil preparation to prevent radiodermatitis: results of a prospective study in nasopharyngeal carcinoma patients. Int J Clin Exp Med. [Internet] 2015 [cited June 14 2016];8(7),11000-6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565279/.
https://www.ncbi.nlm.nih.gov/pmc/article...
,77 Bazire L, Fromantin I, Diallo A, de la Lande B, Pernin V, Dendale R, et al. Hydrosorb® versus control (water based spray) in the management of radio-induced skin toxicity: Results of multicentre controlled randomized trial. Radiother Oncol. 2015;117(2):229-33. doi: 10.1016/j.radonc.2015.08.028
https://doi.org/10.1016/j.radonc.2015.08...
.

Trolamine has been indicated to prevent and treat radiation dermatitis but, to the best of our knowledge, there is no systematic review that evaluated trolamine as a potential topical product to manage skin reactions due to radiotherapy.

Background

Skin reactions may be intensified, according to the treatment plan received, a full high dose, fractional high dose, and the extension of the irradiated area. Chemotherapy and patient related factors, such as age, skin color, smoking habits and obesity also aggravate the skin reactions66 O’Donovan A, Coleman M, Harris R, Herst P. Prophylaxis and management of acute radiation-induced skin toxicity: a survey of practice across Europe and the USA. Eur J Cancer Care (Engl). 2015;24(3):425-35. doi: 10.1111/ecc.12213
https://doi.org/10.1111/ecc.12213...
,88 Manas A, Santolaya M, Ciapa VM, Belinchón B, Tully F. Topical R1 and R2 Prophylactic Treatment of Acute Radiation Dermatitis in Squamous Cell Carcinoma of the Head and Neck and Breast Cancer Patients Treated With Chemoradiotherapy. Eplasty. [Internet] 2015 [cited June 14 2016];15, e25. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485614/
https://www.ncbi.nlm.nih.gov/pmc/article...
.

Topical products are commonly used as alternatives to manage skin reactions due to radiotherapy, although there is insufficient evidence regarding skin care products for the prevention or treatment of radiation dermatitis66 O’Donovan A, Coleman M, Harris R, Herst P. Prophylaxis and management of acute radiation-induced skin toxicity: a survey of practice across Europe and the USA. Eur J Cancer Care (Engl). 2015;24(3):425-35. doi: 10.1111/ecc.12213
https://doi.org/10.1111/ecc.12213...
.

Topical application of emulsions containing trolamine has bee used in clinical practice for more than three decades in Europe and in the United States for the management of radiation dermatitis. Trolamine has the capacity to heal through the recruitment of macrophages to the wound, promoting the growth of granulation tissue99 Del Rosso JQ, Bikowski J. Trolamine-containing topical emulsion: clinical applications in dermatology. Cutis. 2008;81(3):209-14.. Trolamine emulsion is a compound with properties similar to nonsteroidal anti-inflammatory agents and has been considered as a safe and tolerable topical intervention, with low potential to develop contact dermatitis. Trolamine promotes skin hydration and reduces discomfort and pain, which contribute to the non-interruption of treatment99 Del Rosso JQ, Bikowski J. Trolamine-containing topical emulsion: clinical applications in dermatology. Cutis. 2008;81(3):209-14..

The evidence and clinical observations demonstrate the advantages and disadvantages between trolamine and other topical products, including steroidal creams, non-steroidal anti-inflammatory compounds, and antihistamines11 Cui Z, Xin M, Yin H, Zhang J, Han F. Topical use of olive oil preparation to prevent radiodermatitis: results of a prospective study in nasopharyngeal carcinoma patients. Int J Clin Exp Med. [Internet] 2015 [cited June 14 2016];8(7),11000-6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565279/.
https://www.ncbi.nlm.nih.gov/pmc/article...
,1010 Salvo N, Barnes E, van Draanen J, Stacey E, Mitera G, Breen D, et al. Prophylaxis and management of acute radiation-induced skin reactions: a systematic review of the literature. Curr Oncol. [Internet] 2010 [cited June 14 2016];17(4):94-112. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913836/
https://www.ncbi.nlm.nih.gov/pmc/article...
.

The aim of this study is to systematically review the literature about the evidence of trolamine compared to other topical products in the prevention and treatment of acute radiation dermatitis in cancer patients.

Method

Protocol and registration

The reporting of this systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA Checklist1111 Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA Statement. Ann Intern Med. [Internet] 2009 [cited June 14 2016];151(4):264-9. Available from: http://annals.org/aim/article/744664/preferred-reporting-items-systematic-reviews-meta-analyses-prisma-statement
http://annals.org/aim/article/744664/pre...
. The systematic review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD420160328051212 PROPERO. International Prospective Register of Systematic Reviews Available from: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016032805.
http://www.crd.york.ac.uk/PROSPERO/displ...
.

Eligibility criteria

Only original prospective studies in which the objective was to investigate the effects of the use of trolamine as the only active ingredient (without associations) to prevent and treat acute radiation dermatitis compared to other topical products in cancer patients undergoing radiotherapy were eligible. Studies published in Portuguese, English, Spanish, and French were included. There were no restrictions to the year of publication. The age of the participants, sex, previous or concurrent therapies, health status or dosage of treatment was not restricted either.

Studies were excluded for the following reasons: 1. cobalt therapy; 2. studies that compared interventions to chronic radiation dermatitis only; 3. trolamine associated with others compounds; 4. trolamine compared with non-topical products; 5. study design: reviews, letters, conference abstracts, personal opinions, book chapter, retrospective study, descriptive study, case reports or case series.

Information sources and search strategy

Studies were identified using a search strategy adapted for each electronic database, with the aid of a health sciences librarian: CINAHL EBSCO, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, PubMed, and Web of Science. The hand search was performed on the reference lists from the selected articles for any additional references that might have been missed in the electronic search. In addition, a grey literature search was performed using Google Scholar.

We used the following search terms to search PubMed and adapted the strategy for the other databases: (“biafine” OR “triethanolamine” OR “trolamine” OR “trolamine emulsion” OR “emulsion containing trolamine”) AND (“radiodermatitis” OR “dermatitis” OR “radiation dermatitis” OR “radio-dermatitis” OR “skin damage” OR “skin toxicity” OR “skin reaction” OR “skin injuries” OR “radiation reaction” OR “radio-epithelitis” OR “acute skin toxicity” OR “acute skin reaction” OR “acute dermatitis” OR “acute radiodermatitis” OR “acute cutaneous toxicity” OR “acute radiation dermatitis” OR “acute radiation reactions” OR “acute radiation-induced skin reactions” OR “radiation-induced acute skin” OR “radiation induced skin injuries” OR “radiation-induced skin reaction” OR “radiation induced dermatitis” OR “radio-induced damage” OR “radiotherapy-induced skin reactions” OR “radiation skin reactions” OR “radiation-induced skin injuries”).

After obtaining all references, duplicates were excluded by using appropriate software (EndNoteBasic®, Thomson Reuters, USA). All the electronic database searches were undertaken on January 18th, 2016.

Study selection

For the phase of screening and data extraction, ©Covidence (Web-based systematic review tool designed to facilitate the process) was used.

The study selection was conducted in two phases. In phase 1, two investigators (A.G.M. and E.B.F.) independently screened the titles and abstracts of potentially relevant studies and selected articles that appeared to meet the inclusion criteria based on their abstracts. In phase 2, the same reviewers independently read the full-text of all selected articles and excluded studies that did not meet the inclusion criteria. Any disagreements, either in the first or second phases, were resolved by discussion and mutual agreement between the two reviewers. In case a consensus could not be reached, a third author (P.E.D.R.) was involved to make a final decision. Studies that were excluded after full-text assessment and the reasons for their exclusion are listed in Figure 1.

Figure 1
Flow diagram of literature search and selection process. Brasília, DF, Brazil, 2016

Data collection process and items

Two investigators (A.G.M. and E.B.F.) independently collected the data from the selected articles: study characteristics (author(s), year of publication, setting, objectives, methods), population characteristics (sample size, age, irradiated area), intervention characteristics (groups, follow-up period, primary outcomes, radiation dermatitis criteria and statistical analysis), and outcome characteristics (main results). The third author (P.E.D.R.) crosschecked all the retrieved information to make a final decision. If the required data were not complete, attempts were made to contact the authors to retrieve any pertinent missing information.

Risk of bias in individual studies

To assess the risk of bias of the included randomized controlled trials (RCT), the Cochrane Collaboration Risk of Bias Tool1313 Higgins J, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. Available from: www.cochrane-handbook.org.
www.cochrane-handbook.org...
was applied, including judgments about the sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, incomplete outcome data, selective reporting, and other sources of bias. The risk of bias was assessed as low, high or unclear. Two investigators performed this process independently (A.G.M. and E.B.F.). Disagreements between the 2 reviewers were resolved by a third investigator (P.E.D.R.).

Summary measures

The primary outcome was the development of different grades of radiation dermatitis or the reduction of the intensity/degree of reaction. Further measures considered in this review were risk ratio (RR) or risk differences for dichotomous outcomes.

Synthesis of results

The overall data combination of the included studies was performed by a descriptive synthesis. Statistical pooling of data using meta-analysis was planned whenever trials were considered combinable and relatively homogeneous in relation to design, interventions and outcomes. Heterogeneity within studies was evaluated either by considering clinical (differences about participants, type of controls and results), methodological (design and risk of bias) and statistical (effect of studies) characteristics or by using the I2 statistical test. A value from 0 to 40% was considered of not important consistency, between 30 and 60% moderate heterogeneity, whereas 50 to 90% was considered to represent substantial heterogeneity1313 Higgins J, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. Available from: www.cochrane-handbook.org.
www.cochrane-handbook.org...
.

The Cochrane Collaboration´s Review Manager®5 (RevMan 5) was used to summarize the results by means of the Mantel-Haenszel model. The results were presented with 95% confidence intervals (95% CI).

Risk of bias across studies

The quality of evidence and grading of the strength of recommendations was assessed using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE)1414 Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401-6. doi: 10.1016/j.jclinepi.2010.07.015
https://doi.org/10.1016/j.jclinepi.2010....
-1515 Schünemann H, Brożek J, Guyatt G, Oxman A. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group. Available from: www.guidelinedevelopment.org/handbook.
www.guidelinedevelopment.org/handbook...
. The criteria for this assessment were study design, risk of bias, inconsistency, indirectness, imprecision and other considerations. The quality of evidence must be characterized as high, moderate, low, or very low1515 Schünemann H, Brożek J, Guyatt G, Oxman A. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group. Available from: www.guidelinedevelopment.org/handbook.
www.guidelinedevelopment.org/handbook...
.

No funnel plot was constructed to assess the possibility of publication bias because there were few trials per subgroups of meta-analysis.

Results

Study Selection

In phase 1 of study selection, 195 citations were identified across five electronic databases. After the duplicated articles were removed, 138 citations remained. No references from grey literature were added. A thorough screening of the titles and abstracts was completed and 126 references were excluded. A manual search from the reference lists of the identified studies yielded no additional studies. Thus, 12 articles remained for a full-text screening (phase 2). This process led to the exclusion of five studies (Figure 1). In total, seven articles1616 Fisher J, Scott C, Stevens R, Marconi B, Champion L, Freedman GM, et al. Randomized phase III study comparing best supportive care to biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation therapy oncology group (RTOG) 97-13. Int J Radiat Oncol Biol Phys. 2000;48(5):1307-10. doi. http://dx.doi.org/10.1016/S0360-3016(00)00782-3
http://dx.doi.org/10.1016/S0360-3016(00)...

17 Fenig E, Brenner B, Katz A. Topical Biafine and Lipiderm for the prevention of radiation dermatitis: a randomized prospective trial. Oncol Rep. 2001;8(2):305-9. doi. http://dx.doi.org/10.3892/or.8.2.305
http://dx.doi.org/10.3892/or.8.2.305...

18 Pommier P, Gomez F, Sunyach MP, D’Hombres A, Carrie C, Montbarbon X. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004;22(8):1447-53. doi: http://dx.doi.org/10.1200/JCO.2004.07.063
http://dx.doi.org/10.1200/JCO.2004.07.06...

19 Elliott EA, Wright JR, Swann RS, Nguyen-Tân F, Takita C, Bucci MK, et al. 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. J Clin Oncol. 2006;24(13):2092-7. doi: http://dx.doi.org/10.1200/JCO.2005.04.9148
http://dx.doi.org/10.1200/JCO.2005.04.91...

20 Ribet V, Salas S, Levecq JM, Bastit L, Alfonsi M, De Rauglaudre G, et al. Interest of a sterilised anti-burning gel in radiation dermatitis: results of a comparative study. Ann Dermatol Vénéréol. 2008;1:5-10. doi: http://dx.doi.org/10.1016/S0151-9638(08)70091-7.
http://dx.doi.org/10.1016/S0151-9638(08)...

21 Gosselin TK, Schneider SM, Plambeck MA, Rowe K. A Prospective Randomized, Placebo-Controlled Skin Care Study in Women Diagnosed With Breast Cancer Undergoing Radiation Therapy. Oncol Nurs Forum. 2010;37(5):619-26. doi: http://dx.doi.org/10.1188/10.ONF.619-626
http://dx.doi.org/10.1188/10.ONF.619-626...
-2222 Abbas H, Bensadoun RJ. Trolamine emulsion for the prevention of radiation dermatitis in patients with squamous cell carcinoma of the head and neck. Support Care Cancer. 2012;20(1):185-90. doi: http://dx.doi.org/10.1007/s00520-011-1110-3
http://dx.doi.org/10.1007/s00520-011-111...
were selected for data extraction and qualitative synthesis (Figure 2). Figure 1 (flow chart) details the process of identification, inclusion and exclusion of studies with reasons.

Figure 2
Risk of bias assessment for individual studies. Brasília, DF, Brazil, 2016.

Study characteristics

The studies were published in English1616 Fisher J, Scott C, Stevens R, Marconi B, Champion L, Freedman GM, et al. Randomized phase III study comparing best supportive care to biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation therapy oncology group (RTOG) 97-13. Int J Radiat Oncol Biol Phys. 2000;48(5):1307-10. doi. http://dx.doi.org/10.1016/S0360-3016(00)00782-3
http://dx.doi.org/10.1016/S0360-3016(00)...

17 Fenig E, Brenner B, Katz A. Topical Biafine and Lipiderm for the prevention of radiation dermatitis: a randomized prospective trial. Oncol Rep. 2001;8(2):305-9. doi. http://dx.doi.org/10.3892/or.8.2.305
http://dx.doi.org/10.3892/or.8.2.305...

18 Pommier P, Gomez F, Sunyach MP, D’Hombres A, Carrie C, Montbarbon X. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004;22(8):1447-53. doi: http://dx.doi.org/10.1200/JCO.2004.07.063
http://dx.doi.org/10.1200/JCO.2004.07.06...
-1919 Elliott EA, Wright JR, Swann RS, Nguyen-Tân F, Takita C, Bucci MK, et al. 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. J Clin Oncol. 2006;24(13):2092-7. doi: http://dx.doi.org/10.1200/JCO.2005.04.9148
http://dx.doi.org/10.1200/JCO.2005.04.91...
,2121 Gosselin TK, Schneider SM, Plambeck MA, Rowe K. A Prospective Randomized, Placebo-Controlled Skin Care Study in Women Diagnosed With Breast Cancer Undergoing Radiation Therapy. Oncol Nurs Forum. 2010;37(5):619-26. doi: http://dx.doi.org/10.1188/10.ONF.619-626
http://dx.doi.org/10.1188/10.ONF.619-626...
-2222 Abbas H, Bensadoun RJ. Trolamine emulsion for the prevention of radiation dermatitis in patients with squamous cell carcinoma of the head and neck. Support Care Cancer. 2012;20(1):185-90. doi: http://dx.doi.org/10.1007/s00520-011-1110-3
http://dx.doi.org/10.1007/s00520-011-111...
and French2020 Ribet V, Salas S, Levecq JM, Bastit L, Alfonsi M, De Rauglaudre G, et al. Interest of a sterilised anti-burning gel in radiation dermatitis: results of a comparative study. Ann Dermatol Vénéréol. 2008;1:5-10. doi: http://dx.doi.org/10.1016/S0151-9638(08)70091-7.
http://dx.doi.org/10.1016/S0151-9638(08)...
, from 2000 to 2012.

Two studies included patients who also underwent concurrent chemotherapy1919 Elliott EA, Wright JR, Swann RS, Nguyen-Tân F, Takita C, Bucci MK, et al. 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. J Clin Oncol. 2006;24(13):2092-7. doi: http://dx.doi.org/10.1200/JCO.2005.04.9148
http://dx.doi.org/10.1200/JCO.2005.04.91...
,2222 Abbas H, Bensadoun RJ. Trolamine emulsion for the prevention of radiation dermatitis in patients with squamous cell carcinoma of the head and neck. Support Care Cancer. 2012;20(1):185-90. doi: http://dx.doi.org/10.1007/s00520-011-1110-3
http://dx.doi.org/10.1007/s00520-011-111...
. Radical radiotherapy has been reported in five studies1616 Fisher J, Scott C, Stevens R, Marconi B, Champion L, Freedman GM, et al. Randomized phase III study comparing best supportive care to biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation therapy oncology group (RTOG) 97-13. Int J Radiat Oncol Biol Phys. 2000;48(5):1307-10. doi. http://dx.doi.org/10.1016/S0360-3016(00)00782-3
http://dx.doi.org/10.1016/S0360-3016(00)...

17 Fenig E, Brenner B, Katz A. Topical Biafine and Lipiderm for the prevention of radiation dermatitis: a randomized prospective trial. Oncol Rep. 2001;8(2):305-9. doi. http://dx.doi.org/10.3892/or.8.2.305
http://dx.doi.org/10.3892/or.8.2.305...
-1818 Pommier P, Gomez F, Sunyach MP, D’Hombres A, Carrie C, Montbarbon X. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004;22(8):1447-53. doi: http://dx.doi.org/10.1200/JCO.2004.07.063
http://dx.doi.org/10.1200/JCO.2004.07.06...
,2020 Ribet V, Salas S, Levecq JM, Bastit L, Alfonsi M, De Rauglaudre G, et al. Interest of a sterilised anti-burning gel in radiation dermatitis: results of a comparative study. Ann Dermatol Vénéréol. 2008;1:5-10. doi: http://dx.doi.org/10.1016/S0151-9638(08)70091-7.
http://dx.doi.org/10.1016/S0151-9638(08)...
-2121 Gosselin TK, Schneider SM, Plambeck MA, Rowe K. A Prospective Randomized, Placebo-Controlled Skin Care Study in Women Diagnosed With Breast Cancer Undergoing Radiation Therapy. Oncol Nurs Forum. 2010;37(5):619-26. doi: http://dx.doi.org/10.1188/10.ONF.619-626
http://dx.doi.org/10.1188/10.ONF.619-626...
. The use of tamoxifen has been described in only one study, among those including patients with breast cancer1717 Fenig E, Brenner B, Katz A. Topical Biafine and Lipiderm for the prevention of radiation dermatitis: a randomized prospective trial. Oncol Rep. 2001;8(2):305-9. doi. http://dx.doi.org/10.3892/or.8.2.305
http://dx.doi.org/10.3892/or.8.2.305...
.

Two studies1919 Elliott EA, Wright JR, Swann RS, Nguyen-Tân F, Takita C, Bucci MK, et al. 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. J Clin Oncol. 2006;24(13):2092-7. doi: http://dx.doi.org/10.1200/JCO.2005.04.9148
http://dx.doi.org/10.1200/JCO.2005.04.91...
,2222 Abbas H, Bensadoun RJ. Trolamine emulsion for the prevention of radiation dermatitis in patients with squamous cell carcinoma of the head and neck. Support Care Cancer. 2012;20(1):185-90. doi: http://dx.doi.org/10.1007/s00520-011-1110-3
http://dx.doi.org/10.1007/s00520-011-111...
included only head and neck cancer patients, and four studies1616 Fisher J, Scott C, Stevens R, Marconi B, Champion L, Freedman GM, et al. Randomized phase III study comparing best supportive care to biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation therapy oncology group (RTOG) 97-13. Int J Radiat Oncol Biol Phys. 2000;48(5):1307-10. doi. http://dx.doi.org/10.1016/S0360-3016(00)00782-3
http://dx.doi.org/10.1016/S0360-3016(00)...

17 Fenig E, Brenner B, Katz A. Topical Biafine and Lipiderm for the prevention of radiation dermatitis: a randomized prospective trial. Oncol Rep. 2001;8(2):305-9. doi. http://dx.doi.org/10.3892/or.8.2.305
http://dx.doi.org/10.3892/or.8.2.305...
-1818 Pommier P, Gomez F, Sunyach MP, D’Hombres A, Carrie C, Montbarbon X. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004;22(8):1447-53. doi: http://dx.doi.org/10.1200/JCO.2004.07.063
http://dx.doi.org/10.1200/JCO.2004.07.06...
,2121 Gosselin TK, Schneider SM, Plambeck MA, Rowe K. A Prospective Randomized, Placebo-Controlled Skin Care Study in Women Diagnosed With Breast Cancer Undergoing Radiation Therapy. Oncol Nurs Forum. 2010;37(5):619-26. doi: http://dx.doi.org/10.1188/10.ONF.619-626
http://dx.doi.org/10.1188/10.ONF.619-626...
included only breast cancer patients in the sample. Only one2020 Ribet V, Salas S, Levecq JM, Bastit L, Alfonsi M, De Rauglaudre G, et al. Interest of a sterilised anti-burning gel in radiation dermatitis: results of a comparative study. Ann Dermatol Vénéréol. 2008;1:5-10. doi: http://dx.doi.org/10.1016/S0151-9638(08)70091-7.
http://dx.doi.org/10.1016/S0151-9638(08)...
of the selected studies included a heterogeneous sample of patients with different cancer types and irradiated areas: breast and head and neck cancer.

All studies evaluated trolamine as an intervention to prevent radiation dermatitis and only one evaluated trolamine as treatment1919 Elliott EA, Wright JR, Swann RS, Nguyen-Tân F, Takita C, Bucci MK, et al. 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. J Clin Oncol. 2006;24(13):2092-7. doi: http://dx.doi.org/10.1200/JCO.2005.04.9148
http://dx.doi.org/10.1200/JCO.2005.04.91...
. The topical controls were usual care/institution routine1616 Fisher J, Scott C, Stevens R, Marconi B, Champion L, Freedman GM, et al. Randomized phase III study comparing best supportive care to biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation therapy oncology group (RTOG) 97-13. Int J Radiat Oncol Biol Phys. 2000;48(5):1307-10. doi. http://dx.doi.org/10.1016/S0360-3016(00)00782-3
http://dx.doi.org/10.1016/S0360-3016(00)...
,1919 Elliott EA, Wright JR, Swann RS, Nguyen-Tân F, Takita C, Bucci MK, et al. 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. J Clin Oncol. 2006;24(13):2092-7. doi: http://dx.doi.org/10.1200/JCO.2005.04.9148
http://dx.doi.org/10.1200/JCO.2005.04.91...
,2222 Abbas H, Bensadoun RJ. Trolamine emulsion for the prevention of radiation dermatitis in patients with squamous cell carcinoma of the head and neck. Support Care Cancer. 2012;20(1):185-90. doi: http://dx.doi.org/10.1007/s00520-011-1110-3
http://dx.doi.org/10.1007/s00520-011-111...
, calendula1818 Pommier P, Gomez F, Sunyach MP, D’Hombres A, Carrie C, Montbarbon X. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004;22(8):1447-53. doi: http://dx.doi.org/10.1200/JCO.2004.07.063
http://dx.doi.org/10.1200/JCO.2004.07.06...
, water thermal gel2020 Ribet V, Salas S, Levecq JM, Bastit L, Alfonsi M, De Rauglaudre G, et al. Interest of a sterilised anti-burning gel in radiation dermatitis: results of a comparative study. Ann Dermatol Vénéréol. 2008;1:5-10. doi: http://dx.doi.org/10.1016/S0151-9638(08)70091-7.
http://dx.doi.org/10.1016/S0151-9638(08)...
, placebo, Aquaphor®, RadiaCare™2121 Gosselin TK, Schneider SM, Plambeck MA, Rowe K. A Prospective Randomized, Placebo-Controlled Skin Care Study in Women Diagnosed With Breast Cancer Undergoing Radiation Therapy. Oncol Nurs Forum. 2010;37(5):619-26. doi: http://dx.doi.org/10.1188/10.ONF.619-626
http://dx.doi.org/10.1188/10.ONF.619-626...
, Lipiderm and no intervention1717 Fenig E, Brenner B, Katz A. Topical Biafine and Lipiderm for the prevention of radiation dermatitis: a randomized prospective trial. Oncol Rep. 2001;8(2):305-9. doi. http://dx.doi.org/10.3892/or.8.2.305
http://dx.doi.org/10.3892/or.8.2.305...
.

Table 1 summarizes the descriptive characteristics of the studies.

Table 1
Summary of descriptive characteristics of included articles (n=7). Brasília, DF, Brazil, 2016

Risk of bias within studies

The risk of bias was analyzed individually in all studies included. One randomized clinical trial was graded as having a low risk of bias in the six domains assessed2121 Gosselin TK, Schneider SM, Plambeck MA, Rowe K. A Prospective Randomized, Placebo-Controlled Skin Care Study in Women Diagnosed With Breast Cancer Undergoing Radiation Therapy. Oncol Nurs Forum. 2010;37(5):619-26. doi: http://dx.doi.org/10.1188/10.ONF.619-626
http://dx.doi.org/10.1188/10.ONF.619-626...
(Figure 2). Four studies1616 Fisher J, Scott C, Stevens R, Marconi B, Champion L, Freedman GM, et al. Randomized phase III study comparing best supportive care to biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation therapy oncology group (RTOG) 97-13. Int J Radiat Oncol Biol Phys. 2000;48(5):1307-10. doi. http://dx.doi.org/10.1016/S0360-3016(00)00782-3
http://dx.doi.org/10.1016/S0360-3016(00)...
,1919 Elliott EA, Wright JR, Swann RS, Nguyen-Tân F, Takita C, Bucci MK, et al. 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. J Clin Oncol. 2006;24(13):2092-7. doi: http://dx.doi.org/10.1200/JCO.2005.04.9148
http://dx.doi.org/10.1200/JCO.2005.04.91...
-2020 Ribet V, Salas S, Levecq JM, Bastit L, Alfonsi M, De Rauglaudre G, et al. Interest of a sterilised anti-burning gel in radiation dermatitis: results of a comparative study. Ann Dermatol Vénéréol. 2008;1:5-10. doi: http://dx.doi.org/10.1016/S0151-9638(08)70091-7.
http://dx.doi.org/10.1016/S0151-9638(08)...
,2222 Abbas H, Bensadoun RJ. Trolamine emulsion for the prevention of radiation dermatitis in patients with squamous cell carcinoma of the head and neck. Support Care Cancer. 2012;20(1):185-90. doi: http://dx.doi.org/10.1007/s00520-011-1110-3
http://dx.doi.org/10.1007/s00520-011-111...
exhibited an unclear risk of selection bias due to the poor description of the randomization strategy. One of the studies1717 Fenig E, Brenner B, Katz A. Topical Biafine and Lipiderm for the prevention of radiation dermatitis: a randomized prospective trial. Oncol Rep. 2001;8(2):305-9. doi. http://dx.doi.org/10.3892/or.8.2.305
http://dx.doi.org/10.3892/or.8.2.305...
had a high risk of bias due to randomization description of the inclusion of participants in the intervention groups consecutively. The domain “selective reporting” showed predominantly low risk of bias in the evaluation of the studies (100%).

Four studies were classified as high risk of bias because they contained one or more compromised domains1616 Fisher J, Scott C, Stevens R, Marconi B, Champion L, Freedman GM, et al. Randomized phase III study comparing best supportive care to biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation therapy oncology group (RTOG) 97-13. Int J Radiat Oncol Biol Phys. 2000;48(5):1307-10. doi. http://dx.doi.org/10.1016/S0360-3016(00)00782-3
http://dx.doi.org/10.1016/S0360-3016(00)...
-1717 Fenig E, Brenner B, Katz A. Topical Biafine and Lipiderm for the prevention of radiation dermatitis: a randomized prospective trial. Oncol Rep. 2001;8(2):305-9. doi. http://dx.doi.org/10.3892/or.8.2.305
http://dx.doi.org/10.3892/or.8.2.305...
,1919 Elliott EA, Wright JR, Swann RS, Nguyen-Tân F, Takita C, Bucci MK, et al. 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. J Clin Oncol. 2006;24(13):2092-7. doi: http://dx.doi.org/10.1200/JCO.2005.04.9148
http://dx.doi.org/10.1200/JCO.2005.04.91...
-2020 Ribet V, Salas S, Levecq JM, Bastit L, Alfonsi M, De Rauglaudre G, et al. Interest of a sterilised anti-burning gel in radiation dermatitis: results of a comparative study. Ann Dermatol Vénéréol. 2008;1:5-10. doi: http://dx.doi.org/10.1016/S0151-9638(08)70091-7.
http://dx.doi.org/10.1016/S0151-9638(08)...
. Two studies were classified as uncertain risk of bias1818 Pommier P, Gomez F, Sunyach MP, D’Hombres A, Carrie C, Montbarbon X. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004;22(8):1447-53. doi: http://dx.doi.org/10.1200/JCO.2004.07.063
http://dx.doi.org/10.1200/JCO.2004.07.06...
,2222 Abbas H, Bensadoun RJ. Trolamine emulsion for the prevention of radiation dermatitis in patients with squamous cell carcinoma of the head and neck. Support Care Cancer. 2012;20(1):185-90. doi: http://dx.doi.org/10.1007/s00520-011-1110-3
http://dx.doi.org/10.1007/s00520-011-111...
. One of them received positive bias ratings, with low risk of bias in 91% of the evaluated domains1818 Pommier P, Gomez F, Sunyach MP, D’Hombres A, Carrie C, Montbarbon X. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004;22(8):1447-53. doi: http://dx.doi.org/10.1200/JCO.2004.07.063
http://dx.doi.org/10.1200/JCO.2004.07.06...
. Only one study presented low risk of bias in all domains evaluated2121 Gosselin TK, Schneider SM, Plambeck MA, Rowe K. A Prospective Randomized, Placebo-Controlled Skin Care Study in Women Diagnosed With Breast Cancer Undergoing Radiation Therapy. Oncol Nurs Forum. 2010;37(5):619-26. doi: http://dx.doi.org/10.1188/10.ONF.619-626
http://dx.doi.org/10.1188/10.ONF.619-626...
, allowing us to ascribe the results of the study as of increased reliability.

Results of individual studies

The studies used trolamine to prevent or treat radiation dermatitis and reported different results for all 7 articles. Characteristics and results of the included studies are listed in Table 1.

Synthesis of results

Regarding the rating scales, five studies used exclusively the RTOG scale (71.4%)1616 Fisher J, Scott C, Stevens R, Marconi B, Champion L, Freedman GM, et al. Randomized phase III study comparing best supportive care to biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation therapy oncology group (RTOG) 97-13. Int J Radiat Oncol Biol Phys. 2000;48(5):1307-10. doi. http://dx.doi.org/10.1016/S0360-3016(00)00782-3
http://dx.doi.org/10.1016/S0360-3016(00)...

17 Fenig E, Brenner B, Katz A. Topical Biafine and Lipiderm for the prevention of radiation dermatitis: a randomized prospective trial. Oncol Rep. 2001;8(2):305-9. doi. http://dx.doi.org/10.3892/or.8.2.305
http://dx.doi.org/10.3892/or.8.2.305...
-1818 Pommier P, Gomez F, Sunyach MP, D’Hombres A, Carrie C, Montbarbon X. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004;22(8):1447-53. doi: http://dx.doi.org/10.1200/JCO.2004.07.063
http://dx.doi.org/10.1200/JCO.2004.07.06...
,2121 Gosselin TK, Schneider SM, Plambeck MA, Rowe K. A Prospective Randomized, Placebo-Controlled Skin Care Study in Women Diagnosed With Breast Cancer Undergoing Radiation Therapy. Oncol Nurs Forum. 2010;37(5):619-26. doi: http://dx.doi.org/10.1188/10.ONF.619-626
http://dx.doi.org/10.1188/10.ONF.619-626...
-2222 Abbas H, Bensadoun RJ. Trolamine emulsion for the prevention of radiation dermatitis in patients with squamous cell carcinoma of the head and neck. Support Care Cancer. 2012;20(1):185-90. doi: http://dx.doi.org/10.1007/s00520-011-1110-3
http://dx.doi.org/10.1007/s00520-011-111...
, one of them used only NCI-CTC (14,1%)2020 Ribet V, Salas S, Levecq JM, Bastit L, Alfonsi M, De Rauglaudre G, et al. Interest of a sterilised anti-burning gel in radiation dermatitis: results of a comparative study. Ann Dermatol Vénéréol. 2008;1:5-10. doi: http://dx.doi.org/10.1016/S0151-9638(08)70091-7.
http://dx.doi.org/10.1016/S0151-9638(08)...
, and one study used both NCI-CTC and ONS scales to assess the skin reactions of their patients1919 Elliott EA, Wright JR, Swann RS, Nguyen-Tân F, Takita C, Bucci MK, et al. 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. J Clin Oncol. 2006;24(13):2092-7. doi: http://dx.doi.org/10.1200/JCO.2005.04.9148
http://dx.doi.org/10.1200/JCO.2005.04.91...
.

The studies were grouped into subgroups according to the graduation of radiation dermatitis1616 Fisher J, Scott C, Stevens R, Marconi B, Champion L, Freedman GM, et al. Randomized phase III study comparing best supportive care to biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation therapy oncology group (RTOG) 97-13. Int J Radiat Oncol Biol Phys. 2000;48(5):1307-10. doi. http://dx.doi.org/10.1016/S0360-3016(00)00782-3
http://dx.doi.org/10.1016/S0360-3016(00)...
,1818 Pommier P, Gomez F, Sunyach MP, D’Hombres A, Carrie C, Montbarbon X. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004;22(8):1447-53. doi: http://dx.doi.org/10.1200/JCO.2004.07.063
http://dx.doi.org/10.1200/JCO.2004.07.06...

19 Elliott EA, Wright JR, Swann RS, Nguyen-Tân F, Takita C, Bucci MK, et al. 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. J Clin Oncol. 2006;24(13):2092-7. doi: http://dx.doi.org/10.1200/JCO.2005.04.9148
http://dx.doi.org/10.1200/JCO.2005.04.91...

20 Ribet V, Salas S, Levecq JM, Bastit L, Alfonsi M, De Rauglaudre G, et al. Interest of a sterilised anti-burning gel in radiation dermatitis: results of a comparative study. Ann Dermatol Vénéréol. 2008;1:5-10. doi: http://dx.doi.org/10.1016/S0151-9638(08)70091-7.
http://dx.doi.org/10.1016/S0151-9638(08)...

21 Gosselin TK, Schneider SM, Plambeck MA, Rowe K. A Prospective Randomized, Placebo-Controlled Skin Care Study in Women Diagnosed With Breast Cancer Undergoing Radiation Therapy. Oncol Nurs Forum. 2010;37(5):619-26. doi: http://dx.doi.org/10.1188/10.ONF.619-626
http://dx.doi.org/10.1188/10.ONF.619-626...
-2222 Abbas H, Bensadoun RJ. Trolamine emulsion for the prevention of radiation dermatitis in patients with squamous cell carcinoma of the head and neck. Support Care Cancer. 2012;20(1):185-90. doi: http://dx.doi.org/10.1007/s00520-011-1110-3
http://dx.doi.org/10.1007/s00520-011-111...
. Overall, the results of this random-effect meta-analysis demonstrate that there is no difference between the use of trolamine and evaluated controls to prevent radiation dermatitis (RR 1.02, 95% CI: 0.92 - 1.14. I2 = 49%) (Figure 3).

Figure 3
Forest plot of trolamine vs. controls according to the degree of radiation dermatitis

Risk of bias across studies

The quality of the evidence from the outcomes evaluated by the GRADE system was assessed as very low (Figure 4), suggesting very low confidence in the estimated effect based on the outcomes assessed. It means that the true effect is likely to be substantially different from the estimate of effect. The important limitations in the studies and inconsistency were the main factors responsible for the low quality of the evidence from the studies evaluated.

Figure 4
GRADE assessment. Brasília, DF, Brazil, 2016

Discussion

In this review, seven studies evaluating trolamine to prevent or treat radiation dermatitis were included. In four studies1717 Fenig E, Brenner B, Katz A. Topical Biafine and Lipiderm for the prevention of radiation dermatitis: a randomized prospective trial. Oncol Rep. 2001;8(2):305-9. doi. http://dx.doi.org/10.3892/or.8.2.305
http://dx.doi.org/10.3892/or.8.2.305...

18 Pommier P, Gomez F, Sunyach MP, D’Hombres A, Carrie C, Montbarbon X. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004;22(8):1447-53. doi: http://dx.doi.org/10.1200/JCO.2004.07.063
http://dx.doi.org/10.1200/JCO.2004.07.06...
-1919 Elliott EA, Wright JR, Swann RS, Nguyen-Tân F, Takita C, Bucci MK, et al. 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. J Clin Oncol. 2006;24(13):2092-7. doi: http://dx.doi.org/10.1200/JCO.2005.04.9148
http://dx.doi.org/10.1200/JCO.2005.04.91...
,2121 Gosselin TK, Schneider SM, Plambeck MA, Rowe K. A Prospective Randomized, Placebo-Controlled Skin Care Study in Women Diagnosed With Breast Cancer Undergoing Radiation Therapy. Oncol Nurs Forum. 2010;37(5):619-26. doi: http://dx.doi.org/10.1188/10.ONF.619-626
http://dx.doi.org/10.1188/10.ONF.619-626...
, no benefits were shown for the use of trolamine to prevent radiation dermatitis and, in two studies1616 Fisher J, Scott C, Stevens R, Marconi B, Champion L, Freedman GM, et al. Randomized phase III study comparing best supportive care to biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation therapy oncology group (RTOG) 97-13. Int J Radiat Oncol Biol Phys. 2000;48(5):1307-10. doi. http://dx.doi.org/10.1016/S0360-3016(00)00782-3
http://dx.doi.org/10.1016/S0360-3016(00)...
,2020 Ribet V, Salas S, Levecq JM, Bastit L, Alfonsi M, De Rauglaudre G, et al. Interest of a sterilised anti-burning gel in radiation dermatitis: results of a comparative study. Ann Dermatol Vénéréol. 2008;1:5-10. doi: http://dx.doi.org/10.1016/S0151-9638(08)70091-7.
http://dx.doi.org/10.1016/S0151-9638(08)...
there was no difference to prevent radiation dermatitis between trolamine and evaluated controls. Only one study2222 Abbas H, Bensadoun RJ. Trolamine emulsion for the prevention of radiation dermatitis in patients with squamous cell carcinoma of the head and neck. Support Care Cancer. 2012;20(1):185-90. doi: http://dx.doi.org/10.1007/s00520-011-1110-3
http://dx.doi.org/10.1007/s00520-011-111...
showed satisfactory use of trolamine in the prevention of radiation dermatitis, but its results showed benefit only to prevent grade 3 radiation dermatitis.

Trolamine has been considered because of its good tolerability and its ability to moisturize skin and reduce local discomfort. However, it has not been proven that trolamine is a topical skin radioprotective agent99 Del Rosso JQ, Bikowski J. Trolamine-containing topical emulsion: clinical applications in dermatology. Cutis. 2008;81(3):209-14.. Some controls presented greater or similar efficacy when compared to trolamine1616 Fisher J, Scott C, Stevens R, Marconi B, Champion L, Freedman GM, et al. Randomized phase III study comparing best supportive care to biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation therapy oncology group (RTOG) 97-13. Int J Radiat Oncol Biol Phys. 2000;48(5):1307-10. doi. http://dx.doi.org/10.1016/S0360-3016(00)00782-3
http://dx.doi.org/10.1016/S0360-3016(00)...

17 Fenig E, Brenner B, Katz A. Topical Biafine and Lipiderm for the prevention of radiation dermatitis: a randomized prospective trial. Oncol Rep. 2001;8(2):305-9. doi. http://dx.doi.org/10.3892/or.8.2.305
http://dx.doi.org/10.3892/or.8.2.305...

18 Pommier P, Gomez F, Sunyach MP, D’Hombres A, Carrie C, Montbarbon X. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004;22(8):1447-53. doi: http://dx.doi.org/10.1200/JCO.2004.07.063
http://dx.doi.org/10.1200/JCO.2004.07.06...

19 Elliott EA, Wright JR, Swann RS, Nguyen-Tân F, Takita C, Bucci MK, et al. 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. J Clin Oncol. 2006;24(13):2092-7. doi: http://dx.doi.org/10.1200/JCO.2005.04.9148
http://dx.doi.org/10.1200/JCO.2005.04.91...

20 Ribet V, Salas S, Levecq JM, Bastit L, Alfonsi M, De Rauglaudre G, et al. Interest of a sterilised anti-burning gel in radiation dermatitis: results of a comparative study. Ann Dermatol Vénéréol. 2008;1:5-10. doi: http://dx.doi.org/10.1016/S0151-9638(08)70091-7.
http://dx.doi.org/10.1016/S0151-9638(08)...
-2121 Gosselin TK, Schneider SM, Plambeck MA, Rowe K. A Prospective Randomized, Placebo-Controlled Skin Care Study in Women Diagnosed With Breast Cancer Undergoing Radiation Therapy. Oncol Nurs Forum. 2010;37(5):619-26. doi: http://dx.doi.org/10.1188/10.ONF.619-626
http://dx.doi.org/10.1188/10.ONF.619-626...
. According to the meta-analysis, there is no difference between trolamine and controls to prevent radiation dermatitis1616 Fisher J, Scott C, Stevens R, Marconi B, Champion L, Freedman GM, et al. Randomized phase III study comparing best supportive care to biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation therapy oncology group (RTOG) 97-13. Int J Radiat Oncol Biol Phys. 2000;48(5):1307-10. doi. http://dx.doi.org/10.1016/S0360-3016(00)00782-3
http://dx.doi.org/10.1016/S0360-3016(00)...
,1818 Pommier P, Gomez F, Sunyach MP, D’Hombres A, Carrie C, Montbarbon X. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004;22(8):1447-53. doi: http://dx.doi.org/10.1200/JCO.2004.07.063
http://dx.doi.org/10.1200/JCO.2004.07.06...

19 Elliott EA, Wright JR, Swann RS, Nguyen-Tân F, Takita C, Bucci MK, et al. 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. J Clin Oncol. 2006;24(13):2092-7. doi: http://dx.doi.org/10.1200/JCO.2005.04.9148
http://dx.doi.org/10.1200/JCO.2005.04.91...

20 Ribet V, Salas S, Levecq JM, Bastit L, Alfonsi M, De Rauglaudre G, et al. Interest of a sterilised anti-burning gel in radiation dermatitis: results of a comparative study. Ann Dermatol Vénéréol. 2008;1:5-10. doi: http://dx.doi.org/10.1016/S0151-9638(08)70091-7.
http://dx.doi.org/10.1016/S0151-9638(08)...

21 Gosselin TK, Schneider SM, Plambeck MA, Rowe K. A Prospective Randomized, Placebo-Controlled Skin Care Study in Women Diagnosed With Breast Cancer Undergoing Radiation Therapy. Oncol Nurs Forum. 2010;37(5):619-26. doi: http://dx.doi.org/10.1188/10.ONF.619-626
http://dx.doi.org/10.1188/10.ONF.619-626...
-2222 Abbas H, Bensadoun RJ. Trolamine emulsion for the prevention of radiation dermatitis in patients with squamous cell carcinoma of the head and neck. Support Care Cancer. 2012;20(1):185-90. doi: http://dx.doi.org/10.1007/s00520-011-1110-3
http://dx.doi.org/10.1007/s00520-011-111...
.

The skin moisture and the skin reactions from the radiotherapy could be influenced by the number of intervention applications along the day. Some studies instructed the patients to apply the intervention three times a day1616 Fisher J, Scott C, Stevens R, Marconi B, Champion L, Freedman GM, et al. Randomized phase III study comparing best supportive care to biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation therapy oncology group (RTOG) 97-13. Int J Radiat Oncol Biol Phys. 2000;48(5):1307-10. doi. http://dx.doi.org/10.1016/S0360-3016(00)00782-3
http://dx.doi.org/10.1016/S0360-3016(00)...
,1919 Elliott EA, Wright JR, Swann RS, Nguyen-Tân F, Takita C, Bucci MK, et al. 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. J Clin Oncol. 2006;24(13):2092-7. doi: http://dx.doi.org/10.1200/JCO.2005.04.9148
http://dx.doi.org/10.1200/JCO.2005.04.91...
,2222 Abbas H, Bensadoun RJ. Trolamine emulsion for the prevention of radiation dermatitis in patients with squamous cell carcinoma of the head and neck. Support Care Cancer. 2012;20(1):185-90. doi: http://dx.doi.org/10.1007/s00520-011-1110-3
http://dx.doi.org/10.1007/s00520-011-111...
or twice daily1717 Fenig E, Brenner B, Katz A. Topical Biafine and Lipiderm for the prevention of radiation dermatitis: a randomized prospective trial. Oncol Rep. 2001;8(2):305-9. doi. http://dx.doi.org/10.3892/or.8.2.305
http://dx.doi.org/10.3892/or.8.2.305...
,2121 Gosselin TK, Schneider SM, Plambeck MA, Rowe K. A Prospective Randomized, Placebo-Controlled Skin Care Study in Women Diagnosed With Breast Cancer Undergoing Radiation Therapy. Oncol Nurs Forum. 2010;37(5):619-26. doi: http://dx.doi.org/10.1188/10.ONF.619-626
http://dx.doi.org/10.1188/10.ONF.619-626...
or five times a day2020 Ribet V, Salas S, Levecq JM, Bastit L, Alfonsi M, De Rauglaudre G, et al. Interest of a sterilised anti-burning gel in radiation dermatitis: results of a comparative study. Ann Dermatol Vénéréol. 2008;1:5-10. doi: http://dx.doi.org/10.1016/S0151-9638(08)70091-7.
http://dx.doi.org/10.1016/S0151-9638(08)...
. Only one study1818 Pommier P, Gomez F, Sunyach MP, D’Hombres A, Carrie C, Montbarbon X. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004;22(8):1447-53. doi: http://dx.doi.org/10.1200/JCO.2004.07.063
http://dx.doi.org/10.1200/JCO.2004.07.06...
allowed patients to apply the intervention twice a day or more according to the frequence of radiation dermatitis and pain. None of this studies described a relation between the frequence of intervention and control applications and the skin moisture. One of the studies1717 Fenig E, Brenner B, Katz A. Topical Biafine and Lipiderm for the prevention of radiation dermatitis: a randomized prospective trial. Oncol Rep. 2001;8(2):305-9. doi. http://dx.doi.org/10.3892/or.8.2.305
http://dx.doi.org/10.3892/or.8.2.305...
asked patients to start the product application ten days before the onset of radiotherapy, but no contribution was added to prevent radiation dermatitis.

The product quantity in each application was not measured by the studies, except in one of the studies1818 Pommier P, Gomez F, Sunyach MP, D’Hombres A, Carrie C, Montbarbon X. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004;22(8):1447-53. doi: http://dx.doi.org/10.1200/JCO.2004.07.063
http://dx.doi.org/10.1200/JCO.2004.07.06...
in which the mean total number of tubes was 1.62 times more used in the trolamine group than in the calendula group.

Patients considered trolamine use more satisfactory than controls when compared to calendula1818 Pommier P, Gomez F, Sunyach MP, D’Hombres A, Carrie C, Montbarbon X. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004;22(8):1447-53. doi: http://dx.doi.org/10.1200/JCO.2004.07.063
http://dx.doi.org/10.1200/JCO.2004.07.06...
and AquaphorR and RadiaCareR(2121 Gosselin TK, Schneider SM, Plambeck MA, Rowe K. A Prospective Randomized, Placebo-Controlled Skin Care Study in Women Diagnosed With Breast Cancer Undergoing Radiation Therapy. Oncol Nurs Forum. 2010;37(5):619-26. doi: http://dx.doi.org/10.1188/10.ONF.619-626
http://dx.doi.org/10.1188/10.ONF.619-626...
.

Some studies have shown that chemotherapy and tamoxifen increased the intensity of skin reactions in patients undergoing radiotherapy2323 Giro C, Berger B, Bölke E, Ciernik IF, Duprez F, Locati L, et al. High rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: results of a survey in EORTC institutes. Radiother Oncol. 2009;90(2):166-71. doi: http://dx.doi.org/10.1016/j.radonc.2008.09.007
http://dx.doi.org/10.1016/j.radonc.2008....

24 Merlano M, Russi E, Benasso M, Corvò R, Colantonio I, Vigna-Taglianti R, et al. Cisplatin-based chemoradiation plus cetuximab in locally advanced head and neck cancer: a phase II clinical study. Ann Oncol. 2011;22(3):712-7. doi: http://dx.doi.org/10.1093/annonc/mdq412
http://dx.doi.org/10.1093/annonc/mdq412...

25 Studer G, Brown M, Salgueiro EB, Schmückle H, Romancuk N, Winkler G, et al. Grade 3/4 dermatitis in head and neck cancer patients treated with concurrent cetuximab and IMRT. Int J Radiat Oncol Biol Phys. 2011;81(1):110-7. doi: http://dx.doi.org/10.1016/j.ijrobp.2010.05.018
http://dx.doi.org/10.1016/j.ijrobp.2010....
-2626 De Langhe S, Mulliez T, Veldeman L, Remouchamps V, van Greveling A, Gilsoul M, et al. Factors modifying the risk for developing acute skin toxicity after whole-breast intensity modulated radiotherapy. BMC Cancer. 2014;14:711. doi: http://dx.doi.org/10.1186/1471-2407-14-711
http://dx.doi.org/10.1186/1471-2407-14-7...
. Two studies used chemoradiotherapy1919 Elliott EA, Wright JR, Swann RS, Nguyen-Tân F, Takita C, Bucci MK, et al. 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. J Clin Oncol. 2006;24(13):2092-7. doi: http://dx.doi.org/10.1200/JCO.2005.04.9148
http://dx.doi.org/10.1200/JCO.2005.04.91...
,2222 Abbas H, Bensadoun RJ. Trolamine emulsion for the prevention of radiation dermatitis in patients with squamous cell carcinoma of the head and neck. Support Care Cancer. 2012;20(1):185-90. doi: http://dx.doi.org/10.1007/s00520-011-1110-3
http://dx.doi.org/10.1007/s00520-011-111...
and, in one study, tamoxifen was used concomitantly with radiotherapy in breast cancer patients1717 Fenig E, Brenner B, Katz A. Topical Biafine and Lipiderm for the prevention of radiation dermatitis: a randomized prospective trial. Oncol Rep. 2001;8(2):305-9. doi. http://dx.doi.org/10.3892/or.8.2.305
http://dx.doi.org/10.3892/or.8.2.305...
, but these studies did not report significant differences in the skin reactions between the groups using trolamine or controls.

Only one study evaluated the efficacy of trolamine to treat radiation dermatitis, and considered no efficacy of trolamine in head and neck cancer patients1919 Elliott EA, Wright JR, Swann RS, Nguyen-Tân F, Takita C, Bucci MK, et al. 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. J Clin Oncol. 2006;24(13):2092-7. doi: http://dx.doi.org/10.1200/JCO.2005.04.9148
http://dx.doi.org/10.1200/JCO.2005.04.91...
. It is important that other studies evaluate trolamine to treat grade 1 and grade 2 radiation dermatitis, because these grades require products with moisturizing and anti-inflammatory action. One of the studies2222 Abbas H, Bensadoun RJ. Trolamine emulsion for the prevention of radiation dermatitis in patients with squamous cell carcinoma of the head and neck. Support Care Cancer. 2012;20(1):185-90. doi: http://dx.doi.org/10.1007/s00520-011-1110-3
http://dx.doi.org/10.1007/s00520-011-111...
considered that trolamine prevents grade 3 of radiation dermatitis in head and neck cancer patients, but this conclusion is only based on those patients who did not develop grade 3 of radiation dermatitis. Moreover, the non-development of maximum grades of radiation dermatitis depends on extrinsic (total dose, fractionation, radiation energy, volume of treated regions, treatment duration, boost aplication, and treatment site) and intrinsic factors (age, comorbid conditions, skin phototype, and genetic predisposition)2727 Franco P, Potenza I, Moretto F, Segantin M, Grosso M, Lombardo A, et al. Hypericum perforatum and neem oil for the management of acute skin toxicity in head and neck cancer patients undergoing radiation or chemo-radiation: a single-arm prospective observational study. Radiat Oncol. 2014;9:297. doi: http://dx.doi.org/10.1186/s13014-014-0297-0
http://dx.doi.org/10.1186/s13014-014-029...
.

Conclusion

Based on the studies included in this review, trolamine cannot be considered as a standardized product to prevent or treat radiation dermatitis in patients with breast and head and neck cancer. Further well-structured blinded studies using trolamine as a treatment are required to evaluated the moisturizing and anti-inflammatory action.

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    » http://dx.doi.org/10.1007/s00520-011-1110-3
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    Studer G, Brown M, Salgueiro EB, Schmückle H, Romancuk N, Winkler G, et al. Grade 3/4 dermatitis in head and neck cancer patients treated with concurrent cetuximab and IMRT. Int J Radiat Oncol Biol Phys. 2011;81(1):110-7. doi: http://dx.doi.org/10.1016/j.ijrobp.2010.05.018
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    » http://dx.doi.org/10.1186/1471-2407-14-711
  • 27
    Franco P, Potenza I, Moretto F, Segantin M, Grosso M, Lombardo A, et al. Hypericum perforatum and neem oil for the management of acute skin toxicity in head and neck cancer patients undergoing radiation or chemo-radiation: a single-arm prospective observational study. Radiat Oncol. 2014;9:297. doi: http://dx.doi.org/10.1186/s13014-014-0297-0
    » http://dx.doi.org/10.1186/s13014-014-0297-0

Publication Dates

  • Publication in this collection
    2018

History

  • Received
    08 Feb 2017
  • Accepted
    27 May 2017
Escola de Enfermagem de Ribeirão Preto / Universidade de São Paulo Av. Bandeirantes, 3900, 14040-902 Ribeirão Preto SP Brazil, Tel.: +55 (16) 3315-3451 / 3315-4407 - Ribeirão Preto - SP - Brazil
E-mail: rlae@eerp.usp.br