{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T13:01:42Z","timestamp":1762261302767,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NCI Cancer Center Support","award":["P30 CA91842"],"award-info":[{"award-number":["P30 CA91842"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Functional p53 is critical for anti-tumor activity of mitomycin-C. In wild-type TP53 human papillomavirus (HPV)-positive squamous cell carcinoma (SCC) cell lines, mitomycin-C repressed E6 oncoprotein expression and induced p53, p21, and Bax, resulting in apoptosis. In mutant TP53 HPV-negative SCC cell lines, mitomycin-C was inactive. The primary aim of this trial was to determine the objective response rate (ORR) with mitomycin-C among patients with HPV-positive (cohort A) and HPV-negative (cohort B) platinum-refractory, recurrent or metastatic head and neck SCC (RM-HNSCC). Methods: Patients with platinum-refractory RM-HNSCC received mitomycin-C (10 mg\/m2 on day one every five weeks) until discontinuation criteria were met. Tumor response was assessed by RECIST1.1. We hypothesized an ORR of \u226530% (H1) with mitomycin-C (vs. H0 ORR of \u226410%). Using a two-stage Simon phase 2 design for each cohort, 2 or more responses among 12 evaluable patients were required to enroll 23 additional patients. H1 was accepted if 6 or more responses occurred among 35 evaluable patients (power 0.90; one-sided \u03b1 = 0.10). Results: Forty-seven patients were treated with mitomycin-C: 34 in cohort A and 13 in cohort B. Tumor response occurred in 3 of 33 evaluable patients in cohort A (ORR 9.1%, 95%CI: 0\u201319.4) and in 0 of 12 evaluable patients in cohort B. The duration of tumor responses in cohort A was 2.3, 2.5, and 4.5 months. The most common treatment-related AEs of any grade were anemia (96%), fatigue (62%), and thrombocytopenia (40%). No treatment-related deaths occurred. Conclusions: Mitomycin-C had limited activity in HPV-positive, and no activity in HPV-negative, platinum-refractory RM-HNSCC.<\/jats:p>","DOI":"10.3390\/cancers17213568","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T12:13:08Z","timestamp":1762258388000},"page":"3568","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitomycin-C for HPV-Positive and HPV-Negative Platinum-Refractory, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Phase 2 Trial"],"prefix":"10.3390","volume":"17","author":[{"given":"Peter","family":"Oppelt","sequence":"first","affiliation":[{"name":"Alvin J. Siteman Cancer Center, St. Louis, MO 63110, USA"},{"name":"Division of Medical Oncology, Washington University School of Medicine, 660 South Euclid, Campus Box 8056, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5092-8884","authenticated-orcid":false,"given":"Jessica","family":"Ley","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Washington University School of Medicine, 660 South Euclid, Campus Box 8056, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0080-4514","authenticated-orcid":false,"given":"Christine","family":"Auberle","sequence":"additional","affiliation":[{"name":"Alvin J. Siteman Cancer Center, St. Louis, MO 63110, USA"},{"name":"Division of Medical Oncology, Washington University School of Medicine, 660 South Euclid, Campus Box 8056, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1953-9041","authenticated-orcid":false,"given":"Brendan","family":"Knapp","sequence":"additional","affiliation":[{"name":"Alvin J. Siteman Cancer Center, St. Louis, MO 63110, USA"},{"name":"Division of Medical Oncology, Washington University School of Medicine, 660 South Euclid, Campus Box 8056, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesse","family":"Zaretsky","sequence":"additional","affiliation":[{"name":"Alvin J. Siteman Cancer Center, St. Louis, MO 63110, USA"},{"name":"Division of Medical Oncology, Washington University School of Medicine, 660 South Euclid, Campus Box 8056, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8311-5553","authenticated-orcid":false,"given":"Fei","family":"Wan","sequence":"additional","affiliation":[{"name":"Division of Public Health Sciences, Biostatistics Shared Resource, Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Adkins","sequence":"additional","affiliation":[{"name":"Alvin J. Siteman Cancer Center, St. Louis, MO 63110, USA"},{"name":"Division of Medical Oncology, Washington University School of Medicine, 660 South Euclid, Campus Box 8056, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Global Burden of Disease Cancer Collaboration, Fitzmaurice, C., Akinyemiju, T.F., Al Lami, F.H., Alam, T., Alizadeh-Navaei, R., Allen, C., Alsharif, U., Alvis-Guzman, N., and Amini, E. (2018). Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2016: A systematic analysis for the global burden of disease study. 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