Oral or Topical Catechins for Radiation Dermatitis

Introduction Radiation-induced dermatitis (RID), which includes both acute and chronic forms, affects up to 95% of patients undergoing radiation therapy. Despite its high incidence, there are currently no validated prevention and management recommendations specifically for the mexican population. Catechins, particularly epigallocatechin gallate and epicatechin, are emerging as a promising and readily accessible therapeutic option for radiation damage in skin and other organs, including conditions like esophagitis, intestinal injury, and mucositis. Objective This study aims to evaluate the utility of oral or topical catechins in preventing and managing acute and chronic radiation-induced dermatitis in cancer patients, comparing their effectiveness against standard treatment. Material and Methods This will be a randomized, double-blind, phase III clinical trial with a longitudinal and comparative design. Patients will be allocated into two primary study groups: prevention (n=81) and treatment (n=81). Each group will be further divided into four treatment arms: Epigallocatechin gallate (experimental aerosol) Epicatechin (experimental capsule) Saline control arm (aerosol) Microcrystalline cellulose excipient control arm (capsule) All participants across all groups will receive standard care. Study endpoints will include the assessment of utility, toxicity, quality of life, and cosmesis, using various validated scales and scores. Ethics This study adheres to the principles outlined in the Helsinki Declaration (2024), the Nuremberg Code, and Mexico's General Health Law on health research. Given the wide therapeutic margin of the interventions, the study is classified as minimal risk. Statistical Analysis To evaluate the efficacy of the intervention (specifically, the change in the risk of dermatitis and fibrosis), we will calculate the hazard ratio using Cox regression and compare it with the Log-Rank test. Additionally, both fixed and random effects models will be performed and compared using the likelihood ratio test.

Sex

All

Minimum age

18 Years

Maximum age

75 Years

Inclusion Criteria:

* Histopathologically confirmed diagnosis of cancer.
* Complete blood count, blood chemistry, and liver function tests within normal ranges.
* Availability of an anatomopathological report.
* Aged between 18 and 75 years.
* Karnofsky performance status (KPS) score \> 60 or an Eastern Cooperative Oncology Group (ECOG) performance status score \< 3.
* Candidate for radiotherapy with a prescribed dose of ≥40 Gy or its biological equivalent (EQD2).
* Must provide written informed consent to participate in the study.
* Must be able to swallow capsules.
* Must meet one of the following cohort-specific criteria:

  1. Prevention cohort: No clinical evidence of dermatitis at the initiation of radiotherapy.
  2. Treatment cohort: Development of grade 1 dermatitis during radiotherapy, with symptom onset within the last 3 days.

Exclusion Criteria:

* Pregnant or lactating.
* Immunocompromised or on chronic therapy with immunosuppressive or immunomodulatory medications.
* History of chemical burns or unhealed wounds in the intended radiotherapy treatment area.
* Current diagnosis of skin cancer or a known diagnosis of a DNA repair gene defect.
* Prior radiotherapy to the area currently being treated.
* Known allergy to any of the study compounds.
* Currently receiving treatment with bortezomib, sunitinib, ticagrelor, or other antithrombotic agents.

Withdrawal Criteria:

* Adherence to the study intervention is less than 80%.
* Withdrawal of consent.
* Suspension of their radiotherapy sessions secondary to an acute infectious disease or the need for hospitalization

• BACKGROUNDChacko SM, Thambi PT, Kuttan R, Nishigaki I. Beneficial effects of green tea: a literature review. Chin Med. 2010 Apr 6;5:13. doi: 10.1186/1749-8546-5-13. PMID 20370896
• BACKGROUNDOrtiz J, Kestur US, Taylor LS, Mauer LJ. Interaction of environmental moisture with powdered green tea formulations: relationship between catechin stability and moisture-induced phase transformations. J Agric Food Chem. 2009 Jun 10;57(11):4691-7. doi: 10.1021/jf8038583. PMID 19489621
• BACKGROUNDMoreno-Ulloa A , Najera-Garcia N , Hernandez M , Ramirez-Sanchez I , Taub PR , Su Y , Beltran-Partida E , Ceballos G , Dugar S , Schreiner G , Best BM , Ciaraldi TP , Henry RR , Villarreal F . A pilot study on clinical pharmacokinetics and preclinical pharmacodynamics of (+)-epicatechin on cardiometabolic endpoints. Food Funct. 2018 Jan 24;9(1):307-319. doi: 10.1039/c7fo01028a. PMID 29171848
• BACKGROUNDVollmann J, Winau R. Informed consent in human experimentation before the Nuremberg code. BMJ. 1996 Dec 7;313(7070):1445-9. doi: 10.1136/bmj.313.7070.1445. PMID 8973233
• BACKGROUNDWorld Medical Association. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Participants. JAMA. 2025 Jan 7;333(1):71-74. doi: 10.1001/jama.2024.21972. PMID 39425955
• BACKGROUNDHopewell S, Chan AW, Collins GS, Hrobjartsson A, Moher D, Schulz KF, Tunn R, Aggarwal R, Berkwits M, Berlin JA, Bhandari N, Butcher NJ, Campbell MK, Chidebe RCW, Elbourne D, Farmer A, Fergusson DA, Golub RM, Goodman SN, Hoffmann TC, Ioannidis JPA, Kahan BC, Knowles RL, Lamb SE, Lewis S, Loder E, Offringa M, Ravaud P, Richards DP, Rockhold FW, Schriger DL, Siegried NL, Staniszewska S, Taylor RS, Thabane L, Torgerson D, Vohra S, White IR, Boutron I. CONSORT 2025 statement: Updated guideline for reporting randomised trials. PLoS Med. 2025 Apr 14;22(4):e1004587. doi: 10.1371/journal.pmed.1004587. eCollection 2025 Apr.