Basal Cell Carcinoma

Basal cell carcinoma is one of the most biologically logical settings for itraconazole because of the importance of Hedgehog signalling in this disease.

Overview

Itraconazole's Hedgehog-pathway inhibition gives it a particularly strong mechanistic fit in basal cell carcinoma, where blocking the Smoothened (SMO) step of the pathway can slow or shrink tumours.

Key human data

• An open-label phase II trial in 29 patients with basal cell carcinoma treated 19 patients with oral itraconazole, using 200 mg twice daily for 1 month in one cohort and 100 mg twice daily for about 2.3 months in another.

• Itraconazole reduced tumour-cell proliferation measured by Ki-67 by about 45% and reduced Hedgehog-pathway activity measured by GLI1 mRNA by about 65% in tumour biopsies.

• In a subset of patients with multiple unbiopsied tumours, mean tumour area fell by around 24% after treatment.

• In that same subset, four of eight patients had partial responses and four of eight had stable disease, while untreated control tumours did not shrink.

• Case reports and small series suggest similar activity in advanced or metastatic basal cell carcinoma and in combination with standard Hedgehog inhibitors, but these data are still very limited.

Practical interpretation

This is one of the clearest examples of pathway logic and early clinical signal lining up in the same cancer type. Itraconazole hits Hedgehog in the lab and measurably dampens Hedgehog signalling and tumour growth in human basal cell carcinoma.

However, the trial was small and short. Dedicated Hedgehog inhibitors such as vismodegib and sonidegib have stronger evidence and higher response rates, so itraconazole sits as a repurposed, off-label option rather than standard first-line therapy.

References

Open-label, exploratory phase II trial of oral itraconazole for the treatment of basal cell carcinoma
https://pubmed.ncbi.nlm.nih.gov/24493717/

Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth
https://www.sciencedirect.com/science/article/pii/S153561081000070X

Inhibition of the Hedgehog pathway for the treatment of cancer using itraconazole
https://pmc.ncbi.nlm.nih.gov/articles/PMC6711563/

Old drug, new target: Itraconazole and basal cell carcinoma
https://jpmsonline.com/article/jpms-volume-5-issue-1-pages21-22-ed/

Itraconazole in the treatment of basal cell carcinoma: case-based experience and combinations with vismodegib
https://onlinelibrary.wiley.com/doi/10.1111/ajd.13655