Antifungal Drugs Active Against Both ... - Advanced Prostate...

There are several mechanisms of actions: Hedgehog inhibition (stemness, proliferation), VEFG inhibition (angiogenesis), Autophagy, Multi-drug resistance.

Schwah5 years ago

Tall Allen, lots of is here would like you to weigh in on this subject. Your objectivity to the science of it all is always sobering.

Schwah

Tall_Allen• in reply toSchwah5 years ago

This stuff has known serious toxicity, so it would have to have some real benefit to have a therapeutic ratio worth pursuing. Unfortunately, it doesn't. It only seems to have any effect at high doses at which the toxicities were serious, and even then, the effect is "modest."

"High-dose itraconazole (600 mg/day) has modest antitumor activity in men with metastatic CRPC...Common toxicities included fatigue, nausea, anorexia, rash, and a syndrome of hypokalemia, hypertension, and edema."

ncbi.nlm.nih.gov/pmc/articl...

"However, the magnitude of effect is modest, and treatment carries risk of toxicities associated with mineralocorticoid excess...The most common adverse events were edema (52%), fatigue (38%), hypertension (24%), and hypokalemia (24%).

ncbi.nlm.nih.gov/pubmed/303...

A related drug, ketoconazole, was used for years before Zytiga became available. They inhibit an enzyme used in the adrenal glands to synthesize androgens. They have high liver toxicity. Zytiga was much more powerful. It is possible that some of the side effects would be mitigated by replacement prednisone. The claim is that it inhibits "hedgehog signaling" - a growth pathway for cancer. Usually, when one pathway is blocked, the cancer just finds another pathway. There are trials for more powerful and specific hedgehog signalling inhibitors (e.g., cyclopamine, Vismodegib, Sonidegib)

In fact, I tried it (at lower doses) for basal cell carcinoma. It did nothing for me, but perhaps a higher dose might. I decided to avoid the side effects and just get them scraped off.

tallguy2• in reply toTall_Allen5 years ago

Thanks for posting your analysis.

vandy695 years ago

Dr. Snuffy Myers put me on high dose Ketoconazole early in my journey. Both he and CVS missed the interaction with Warfarin which nearly killed me. For blood clotting, your INR should be 2. After these 2 drugs together, my INR was 13!

If I had bumped my head, I would have bled to death, but did have good looking toenails.

Best Wishes. Never Give In.

Mark, Atlanta

cesanon• in reply tovandy695 years ago

What was Myers' rationale for choosing to use Ketoconazole.

He had a fair number of treatment options. What was the reason he thought it was most appropriate in you case?

vandy69• in reply tocesanon5 years ago

He used high dose Ketoconozole with me after Zytiga failed. I had about a 1 1/2 run with Zytiga.

I was metastatic at diagnosis with mets in many lymph nodes, but no bone involvement.

After Keto failed, I moved to Xtandi. In the background for about 2 1/2 years, I self injected daily with Leukine.

Never Give In.

Mark