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Cancer research has been making great strides, what with improved earlier detection methods, more focused treatments based on genetic markers, immunotherapies etc. However, we still have a long way to go, and most cancers present a great challenge. In the meantime, a number of old drugs have been identified which have been more recently discovered to offer benefits in cancer treatment. Thus, we refer to these drugs as ‘repurposed drugs’ – i.e. drugs that were originally created, studied, and FDA-approved for another purpose, but then were found to have benefit for a different usage. Many drugs on the market are used in this way as repurposed drugs – for example, duloxetine, originally approved for treatment of depression, has also been found to be useful in the treatment of diabetic neuropathy and fibromyalgia. Similarly, a number of drugs are being repurposed and studied for usage in cancer treatment. When we can identify drugs that are relatively well-tolerated, and that have been shown in-vitro to reduce cancer cell growth, or shown in-vivo to offer improved survival times, these are important to keep an eye on and may warrant further research or may be worth implementing as part of an integrated cancer treatment plan to improve patient outcomes.
Itraconazole
Itraconazole is an anti-fungal drug, used for treatment of fungal diseases, from those as simple as toenail fungal infections to more serious diseases like chronic fungal lung infections, including blastomycosis, histoplasmosis, aspergillosis, and coccidiodomycosis. It should be used with caution in those with heart failure or those at risk of heart failure, and those with impaired liver function, and there rarely are toxicities associated with its use, which may affect the heart and liver. However, it is usually well-tolerated. Its potential benefits in cancer treatment are based on its actions against angiogenesis (the growth of new blood vessels, which cancerous tumors require for survival and growth), and against the growth signalling pathway called Hedgehog pathway.
There have already been a number of studies showing benefit of using oral itraconazole in combination with other cancer medications. Let’s take a look at a few of note:
One phase 2 study on castration-resistant prostate cancer showed that those taking the higher dose of itraconazole went longer without progression of cancer, with a median progression free survival (PFS) of 36 weeks vs 12 weeks for those taking the lower dose.
A phase 2 study on non-small cell lung cancer (NSCLC), comparing patients just on pemetrexed (a common medication for NSCLC) vs those on itraconazole + pemetrexed, showed that those on the combined regimen had had a median overall survival (OS) of 32 months, compared with the group on pemetrexed alone, whose median OS was 8 months. Granted, this was a small study of only 23 patients, so larger studies are needed to get a better picture of the benefits here.
In a study done retrospectively on patients with relapse of a type of ovarian cancer called clear cell carcinoma, 32 percent of those who received chemotherapy plus itraconazole had a response to their therapies, while only 11% of those who received chemotherapy without itraconazole had a response. The median overall survival for the combination group was 642 days, compared with only 139 days for those using chemotherapy alone.
So far, research suggests itraconazole may have benefit for NSCLC, breast cancer, pancreatic cancer, basal cell carcinoma, ovarian cancer, breast cancer, prostate cancer, and glioblastoma. There has also been a case report of one patient’s complete resolution of mycosis fungoides – a form of cutaneous T-cell lymphoma – using only oral itraconazole.(1)
In addition, there are multiple other old drugs that are being studied for their actions on cancer:
Rapamycin – this drug is often used long-term for people that have received transplants, to prevent transplant rejection. However, because of its effects on the mTOR pathway which promotes cancer cell growth , rapamycin and molecules that are similar to rapamycin have a potential role in treatment of cancer. While rapamycin alone is not sufficient to halt cancer, there may be a combination of treatments that include rapamycin or a rapamycin-like drug which together might be effective. For cancers that are highly dependent on mTOR signalling.(2) Interestingly, they may also have benefit in the treatment of aging in general. Some doctors are using it, together with other drugs, as part of an anti-aging program. I have seen great benefits using rapamycin for this purpose.
Modulating the tumor microenvironment:
Cancer cells tend to create a lot of acidity in the form of protons, which they must then export outside the cell into the surrounding fluid in order to survive and proliferate. This acidity contributes to tumor aggressiveness, and suppresses the immune system, reducing its ability to fight the cancer. There are various drugs that interfere with this ability of cancer cells to export the acidic protons, and thus may be useful in fighting cancer. This includes proton pump inhibitors (PPI’s) such as lansoprazole or omeprazole, carbonic anhydrase inhibitors such as acetazolamide, and others. So far, in human trials, we have seen improved outcomes when combining PPI’s with chemotherapy, in metastatic breast cancer, colorectal cancer, and osteosarcomas. In animals, they have been shown to reverse resistance to chemotherapy for lymphoma, melanoma, and squamous cell carcinoma.
Moreover, in-vitro studies showed that a combination approach, using multiple drugs that each block the cancer cell’s ability to export the acidic proton from the cell in a different way, was shown to be even more effective than any of the drugs on their own.(3) This research paves the way for future experimentation using these mechanisms to improve cancer outcomes.
At Vitality Integrative Medicine, an integrative medicine clinic in Sherman Oaks, Los Angeles, Dr. Jeremy Fischer determines what repurposed drugs may benefit patients, in an integrative cancer treatment model. We also make use of other treatments for cancer, based on individual patient needs, such as high dose IV vitamin C, lifestyle and dietary therapies, and targeted natural supplements.
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Pantziarka P, Sukhatme V, Bouche G, Meheus L, Sukhatme VP. Repurposing Drugs in Oncology (ReDO)-itraconazole as an anti-cancer agent. Ecancermedicalscience. 2015;9:521. Published 2015 Apr 15. doi:10.3332/ecancer.2015.521
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Ballou LM, Lin RZ. Rapamycin and mTOR kinase inhibitors. J Chem Biol. 2008;1(1-4):27–36. doi:10.1007/s12154-008-0003-5
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Iessi E, Logozzi M, Mizzoni D, Di Raimo R, Supuran CT, Fais S. Rethinking the Combination of Proton Exchanger Inhibitors in Cancer Therapy. Metabolites. 2017;8(1):2. Published 2017 Dec 23. doi:10.3390/metabo8010002
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