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

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.