Open-Label, Exploratory Phase II Trial of Oral Itraconazole for the Treatment of Basal Cell Carcinoma
Open accessAbstract
Purpose: Itraconazole, a US Food and Drug Administration–approved antifungal drug, inhibits the Hedgehog (HH) signaling pathway, a crucial driver of basal cell carcinoma (BCC) tumorigenesis, and reduces BCC growth in mice. We assessed the effect of itraconazole on the HH pathway and on tumor size in human BCC tumors. Patients and Methods: Patients with ≥ one BCC tumor > 4 mm in diameter were enrolled onto two cohorts to receive oral itraconazole 200 mg twice per day for 1 month (cohort A) or 100 mg twice per day for an average of 2.3 months (cohort B). The primary end point was change in biomarkers: Ki67 tumor proliferation and HH activity (GLI1 mRNA). Secondary end points included change in tumor size in a subset of patients with multiple tumors. Results: A total of 29 patients were enrolled, of whom 19 were treated with itraconazole. Itraconazole treatment was associated with two adverse events (grade 2 fatigue and grade 4 congestive heart failure). Itraconazole reduced cell proliferation by 45% (P = .04), HH pathway activity by 65% (P = .03), and reduced tumor area by 24% (95% CI, 18.2% to 30.0%). Of eight patients with multiple nonbiopsied tumors, four achieved partial response, and four had stable disease. Tumors from untreated control patients and from those previously treated with vismodegib showed no significant changes in proliferation or tumor size. Conclusion: Itraconazole has anti-BCC activity in humans. These results provide the basis for larger trials of longer duration to measure the clinical efficacy of itraconazole, especially relative to other HH pathway inhibitors.
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In clinical studies, itraconazole has been used as an anti-tumor medication to treat non-small cell lung cancer (NSCLC), prostate cancer, and basal cell carcinoma (BCC).
“In clinical studies, ITZ has been used as an anti-tumor medication to treat non-small cell lung cancer (NSCLC),43 prostate cancer,40 and basal cell carcinoma (BCC).44”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [44]
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- Authors
- Kim, D. J., Kim, J., Spaunhurst, K., Montoya, J., Khodosh, R., Chandra, K., Fu, T., Gilliam, A., Molgo, M., Beachy, P. A., & Tang, J. Y.
- Affiliations
- Palo Alto Medical Foundation (US)
- Daniel J. Kim, James Kim, Katrina Spaunhurst, Rita Khodosh, Kalyani Chandra, Teresa Fu, Philip A. Beachy, and Jean Y. Tang, Stanford University, Stanford; Anita Gilliam, Palo Alto Medical Foundation, Palo Alto, CA; James Kim, University of Texas Southwestern, Dallas, TX; Javier Montoya and Monserrat Molgo, Universidad Católica de Chile, Santiago, Chile.
- Venue
- Journal of Clinical Oncology
- Published
- 2014-03-10
- Volume
- 32
- Issue
- 8
- Pages
- 745-751
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2138305199
- Cited by
- 289
- References
- 23
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 14 · 2023: 22 · 2022: 26 · 2021: 16 · 2020: 27 · 2019: 25 · 2018: 26 · 2017: 23 · 2016: 25 · 2015: 32 · 2014: 21 · 2013: 1 · 2012: 1
- FWCI
- 13.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Damon Runyon Cancer Research Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Health Sciences › Medicine › Epidemiology › Nonmelanoma Skin Cancer Studies
- Health Sciences › Medicine › Dermatology › Cancer and Skin Lesions
- Keywords
- itraconazole, basal cell carcinoma, Hedgehog signaling, tumor shrinkage, vismodegib, multiple tumors
- MeSH terms
- Zinc Finger Protein GLI1, Administration, Oral, Aged, Aged, 80 and over, Antineoplastic Agents, California, Basal Cell Carcinoma, Chile, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Remission Induction, RNA, Messenger, Skin Neoplasms, Time Factors, Transcription Factors, Biomarkers, Tumor, Treatment Outcome, Itraconazole, Disease Progression, Ki-67 Antigen, Tumor Burden, Cell Proliferation
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