Pilot trial of topical MTS‑01 application to reduce dermatitis in patients receiving chemoradiotherapy for stage I‑III carcinoma of the anal canal

Citrin,Deborah; Valle,Luca; Camphausen,Kevin; Cooley‑Zgela,Theresa; Smart,Deedee; Yao,Michael; Mitchell,James B.; Thompson,William; Sereti,Irini; Uldrick,Thomas

doi:10.3892/ijo.2022.5358

Pilot trial of topical MTS‑01 application to reduce dermatitis in patients receiving chemoradiotherapy for stage I‑III carcinoma of the anal canal

Authors:
- Deborah Citrin
- Luca Valle
- Kevin Camphausen
- Theresa Cooley‑Zgela
- Deedee Smart
- Michael Yao
- James B. Mitchell
- William Thompson
- Irini Sereti
- Thomas Uldrick
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Affiliations: Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA, Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA 90045, USA, Gastroenterology and Hepatology Section, Washington DC VA Medical Center, Washington, DC 20422, USA, Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA, Laboratory of Immunoregulation, NIAID, Bethesda, MD 20814, USA, HIV and AIDS Malignancy Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA
Published online on: April 15, 2022 https://doi.org/10.3892/ijo.2022.5358
Article Number: 68

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Abstract

The purpose of the present trial was to determine the feasibility of the daily topical application of the piperidine nitroxide, MTS‑01, combined with chemoradiotherapy in the treatment of patients with anal carcinoma. The secondary study endpoints were the description of the effects of this agent on skin toxicity and rectal‑associated lymphoid tissue. The participants received radiotherapy concurrent with mitomycin‑C and 5‑fluorouracil for carcinoma of the anal canal. MTS‑01 was applied to the bilateral inguinal area and the gluteal cleft. Dermatologic and non‑dermatologic toxicity was graded throughout the treatment period. Circulating lymphocytes were serially collected for phenotyping. Rectal mucosal snag biopsies were collected at baseline and at 1 year of follow‑up. A total of 5 patients received topical MTS‑01. Adverse events attributed to MTS‑01 included asymptomatic grade 1 hypoglycemia and grade 1‑2 diarrhea. Dermatitis within untreated, radiated skin was not more severe than dermatitis in MTS‑01‑treated, unirradiated skin. Circulating CD4⁺ lymphocyte suppression was noted at >1 year following treatment in human immunodeficiency virus‑negative participants. CD4⁺ lymphocytes remained suppressed in the irradiated rectal mucosa at 1 year, whereas the CD8⁺ lymphocyte numbers recovered or increased. On the whole, the present study demonstrates that the MTS‑01 topical application was tolerable with minimal toxicity. Chemoradiation for anal cancer led to prolonged CD4⁺ lymphocytopenia in the circulation and gut mucosa.

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