Straight Through the (tumor) Heart!
Ahhhh Ronnie James Dio, classic. Well worth your time, especially his first album in Rainbow, Ritchie Blackmore’s Rainbow. Chefs kiss. Anyways, back to cancer, the skin kind. It’s so interesting the many treatment option there are for diseases in general and skin cancers (SCs) specifically. Radiation, image guided radiation, Mohs, excision, topical chemo agents, cryotherapy, ED&C, and more. We also now have FDA approved oral treatments to prevent the further growth of, and sometimes shrink nasal cell carcinoma (BCC).
As someone who seems to take forever for any cut to heal, I like this. I also like helping Doc do the Mohs so I’m glad that is still popular but, for those who have contraindications to surgery, or lack the desire to go through that (and myriad other reasons) this is appealing. Fluorourocil, diclofenac, imiquomod are all topical methods but only approved for superficial SCs. Radiation takes a big time commitment and transportation costs. Who likes to have a chunk of skin removed? Not I. Electrodessication and curettage doesn’t look or sound fun. While those (minus radiation) also have lower cure rates like cryotherapy. Ke garne?
I’m going to start with looking at itraconazole for skin cancers. This is a common scenario, a patient (retired farmer usually) comes in and has a few BCC diagnosed. Upon return to discuss treatment options, more suspicious lesions are found and what do you know? BCC my old nemesis. I really do have compassion and sympathy for people who are unable to fully care for themselves, be it from a disease or age related degeneration. I can’t imagine being in that position and not being able to provide wound care for anywhere from 1 to a billion or more biopsy/excision sites.
Wait just a gol darn minute. Isn’t itraconazole an antifungal drug? Yessir tis true. I am not going to do this justice, cancer pathways are not my forte (yet) but here we go. There have been studies (linked below) that have examined the effect of Itraconazole on skin, breast, lung, and ovarian cancer. Why? This is pretty cool. Itraconazole (IT from here on out) has antiangiogenic effect, which means it slows or halts the development of new blood vessels. Cancer is similar to the rest of our tissues in that it needs nutrients to grow and thrive and mutations in certain genes can lead to angiogenesis, which is the development of blood vessels. The cancer makes its own blood supply in a way.
OK, so IT can help to starve the cancers. Could this be used topically for telangectasias or cosmetic purposes? This was shown, in combination with more traditional cancer treatments, to increase the progression free survival and overall survival for non-small-cell lung cancer and ovarian cancer. Super duper cool. What about skin cancers? For this foe, IT seems to work on hedgehog (HH) pathways. Don't ask me what this means, but it is the same MOA as sonidegib and vismodegib, two of the newest oral BCC medications. HH pathways do magic and help cells properly differentiate during development, when this is not working properly, then cancer can be a consequence. Blocking that HH pathways helps to slow, stop, or reduce the spread and size of certain cancers.
So IT works on this MOA and blood vessel formation. Several case studies have looked at the efficacy of PO IT for BCC and cutaneous squamous cell carcinoma (cSCC) with promising results. A gentleman with a 15 year old BCC was treated surgically and with radiation but recurrence occurred. He was started on IT 200mg PO BID, then reduced to 100mg PO BID and showed a halting of tumor growth, at 15 months the lesion began to heal over (you should see the article for some perspective). When discontinued however, the cancer began progressing again and metastasized. In other studies, IT halted progression of metastatic BCC in the lungs, and reduced the size of cutaneous lesions by 24%.
Why do I care? Like I said, people do not like to be cut up and new drugs can cost a literal kidney. I know that IT is less than the asking price of over $10,000 for some newer drugs regardless of insurance coverage. There are patients who may just be tired of surgical interventions or who cannot undergo the surgery, maybe they are on hospice and simply do not want their BCC to become an open sore. Why shouldn't we use this? Let me know. And before you say it, side effect and the impact of other organs is key to safe use. This older population generally has more polypharmacy. Either way, IT 100-200mg PO BID for BCC and maybe cSCC (it is also being looked at for melanoma) might be a winning ticket for some patients.
Love y'all, please share this and the podcast. Peace out.
Itraconazole exerts its anti-melanoma effect by suppressing Hedgehog, Wnt, and PI3K/mTOR signaling pathways by Liang et al., in Oncotarget from April 2017.
Open-label, exploratory phase II trial of oral itraconazole for the treatment of basal cell carcinoma by Kim et al., in the Journal of Clinical Oncology March 2014.
Phase 2 study of pemetrexed and itraconazole as second-line therapy for metastatic nonsquamous non-small-cell lung cancer by Rudin et al., in the Journal of Thoracic Oncology May 2013.
Impact of combination chemotherapy with itraconazole on survival of patients with refractory ovarian cancer by Tsubamoto et al., in Anticancer Research May 2014.
Itraconazole in the treatment of basal cell carcinoma: A case-based review of the literature by Hiu-Kan Ip and McKerrow from the Australasian Journal of Dermatology August 2021.
Itraconazole—A New Player in the Therapy of Advanced Basal Cell Carcinoma: A Case Report by Ciazynska et al., in JCO Oncology Practice August 2020.
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