At what dose does ivermectin exhibit anti-cancer effects?

Ivermectin's Anti-Cancer Effects: Dose Requirements

Ivermectin has demonstrated anti-cancer effects in laboratory studies at concentrations of 5-20 μM, which is significantly higher than the standard clinical dose used for parasitic infections (200 μg/kg), making these anti-cancer effects unlikely to be achievable at currently approved therapeutic doses. 1, 2

Evidence for Anti-Cancer Activity

• Ivermectin has shown antitumor effects in preclinical studies at concentrations of 5 μM in multiple cancer cell lines, with breast cancer (MDA-MB-231, MDA-MB-468, MCF-7) and ovarian cancer (SKOV-3) cell lines being most sensitive 1
• In laboratory studies, ivermectin blocked the oncogenic kinase PAK1 in human ovarian cancer and NF2-deficient Schwannoma cell lines with an IC50 between 5-20 μM depending on cell lines 2
• Ivermectin demonstrated potential to reverse drug resistance in cancer cells through inhibition of the EGFR/ERK/Akt/NF-κB pathway at low doses that did not induce obvious cytotoxicity 3
• Gemcitabine-resistant cholangiocarcinoma cells showed sensitivity to ivermectin treatment in vitro, with dose-dependent inhibition of cell proliferation and colony formation 4

Dose Considerations and Clinical Context

• The standard clinical dose of ivermectin for approved parasitic infections is 200 μg/kg orally, which is significantly lower than concentrations needed for anti-cancer effects 5
• For context, the therapeutic dose of ivermectin for scabies treatment is 200 μg/kg orally, repeated in 2 weeks, which is well below the concentrations used in cancer research 5
• For severe cases of crusted scabies, higher frequency dosing is used (200 μg/kg on days 1,2,8,9, and 15, with possible additional treatment on days 22 and 29), but still at the same 200 μg/kg concentration 5
• The safety of multiple doses of ivermectin in patients with severe liver disease is not well established, which could be a concern for cancer patients with hepatic involvement 5, 6

Clinical Translation Challenges

• The concentrations showing anti-cancer effects in laboratory studies (5-20 μM) would require doses much higher than those currently approved for human use 1, 2
• There is a significant gap between laboratory findings and clinical application, with no established clinical protocols for using ivermectin as an anti-cancer agent 7
• A study from Ecuador noted that some cancer patients were using ivermectin as an alternative therapy alongside conventional treatments, but medical specialists did not recommend this practice due to lack of scientific evidence for human application 7
• Current medical guidelines do not support the use of ivermectin for cancer treatment, and the Infectious Diseases Society of America specifically recommends against ivermectin use even for COVID-19 treatment due to insufficient evidence of benefit 5

Important Caveats

• The anti-cancer effects observed in laboratory studies have not been validated in rigorous clinical trials 7
• Achieving the concentrations used in laboratory studies (5-20 μM) would likely require doses that exceed current safety parameters established for ivermectin 1, 2
• Self-medication with ivermectin for cancer treatment is not supported by clinical evidence and could potentially interfere with established cancer therapies 7
• The safety profile of ivermectin at doses that might achieve anti-cancer effects has not been established 6