Use of chloroquine and clemizole compounds for treatment of inflammatory and cancerous conditions
Disclosed herein are methods for use of R-chloroquine or clemizole or combinations of R-chloroquine and clemizole for the treatment of a subject in need thereof. Uses include methods of treating inflammatory′ conditions, treating liver cancer or reducing the risk of developing liver cancer in a subject. Uses also include methods of treating non-alcoholic steatohepatitis in a subject.
1. A method of treating a subject who has been diagnosed with liver cancer, comprising:
administering to the subject an effective amount of clemizole, a deuterated analog of clemizole, or a clemizole metabolite; and a chemotherapeutic agent.
2. The method of claim 1 , wherein the liver cancer is hepatocellular carcinoma.
3. The method of claim 1 , wherein the result of the treatment is shrinking the tumor, inhibiting growth of the tumor, increasing time to progression of the tumor, prolonging disease-free survival of the subject, decreasing metastases, increasing the progression-free survival of the subject, or increasing overall survival of the subject.
4. The method of claim 1 , further comprising administering to the subject an effective amount of an anti-viral drug, wherein the anti-viral drug is an interferon, a nucleoside analog, a direct acting antiviral, interferon alfa-2b, Peginterferon alfa-2a, entecavir, lamivudine, adefovir, telbivudine, tenofovir, sofosbuvir, ledipasvir, ombitasvir, paritaprevir, ritonavir, dasabuvir, grazoprevir, elbasvir, asunaprevir, daclatasvir, or beclabuvir.
5. The method of claim 1 , further comprising administering an effective amount of an inhibitor of CYP3A4.
6. The method of claim 1 , wherein the chemotherapeutic agent is selected from the group consisting of: an alkylating agent, an anti-metabolite, an immunotherapy, a cancer vaccine, an antibody, a kinase inhibitor, an angiogenesis inhibitor, an anti-tumor antibiotic, a topoisomerase inhibitor, a hormonal therapy, a mitotic inhibitor, a nitrogen mustard, a tyrosine kinase inhibitor, an anti-microtubule agent, a histone deacetylase inhibitor, a proteasome inhibitor, and a photodynamic therapy agent.
7. A method of treating a subject who has been diagnosed with liver cancer, comprising:
administering to the subject an effective amount of clemizole, a deuterated analog of clemizole, or a clemizole metabolite,
wherein the effective amount is 200-500 mg administered once daily, twice daily, or thrice daily.
8. The method of claim 7 , wherein the liver cancer is hepatocellular carcinoma.
9. The method of claim 7 , wherein the result of the treatment is shrinking the tumor, inhibiting growth of the tumor, increasing time to progression of the tumor, prolonging disease-free survival of the subject, decreasing metastases, increasing the progression-free survival of the subject, or increasing overall survival of the subject.
10. The method of claim 7 , further comprising administering to the subject an effective amount of an anti-viral drug, wherein the anti-viral drug is an interferon, a nucleoside analog, a direct acting antiviral drug, interferon alfa-2b, Peginterferon alfa-2a, entecavir, lamivudine, adefovir, telbivudine, tenofovir, sofosbuvir, ledipasvir, ombitasvir, paritaprevir, ritonavir, dasabuvir, grazoprevir, elbasvir, asunaprevir, daclatasvir, or beclabuvir.
11. The method of claim 7 , wherein the effective amount is at least 200 mg administered once daily, twice daily, or thrice daily.
12. The method of claim 7 , wherein the effective amount is at least 300 mg administered once daily, twice daily, or thrice daily.
13. The method of claim 7 , wherein the effective amount is at least 400 mg administered once daily, twice daily, or thrice daily.
14. The method of claim 7 , wherein the effective amount is at least 500 mg administered once daily or no more than thrice daily.
15. The method of claim 7 , wherein clemizole, the deuterated analog of clemizole, or the clemizole metabolite is administered for greater than 2 months.
16. The method of claim 7 , wherein clemizole, the deuterated analog of clemizole, or the clemizole metabolite is administered for greater than 3 months.
17. The method of claim 7 , wherein clemizole, the deuterated analog of clemizole, or the clemizole metabolite is administered for greater than 4 months.
18. A method of treating a subject who has been diagnosed with liver cancer, comprising:
administering to the subject an effective amount of clemizole, a deuterated analog of clemizole, or a clemizole metabolite.
19. A method of preventing liver cancer development in a subject at risk for developing liver cancer, comprising:
administering to the subject an effective amount of clemizole, a deuterated analog of clemizole, or a clemizole metabolite,
wherein the subject has been diagnosed with non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), Hepatitis B infection, or cirrhosis of the liver.
20. The method of claim 19 , wherein said liver cancer is hepatocellular carcinoma.
21. The method of claim 19 , wherein the subject has been diagnosed with NASH.
22. The method of claim 19 , wherein the subject has been diagnosed with NAFLD.
23. The method of claim 19 , wherein the result of said prevention is prolonging the period of cancer-free survival or overall survival.
24. The method of claim 19 , further comprising administering to said subject an effective amount of an anti-viral drug, wherein the anti-viral drug comprises an interferon, a nucleoside analog, a direct acting antiviral, interferon alfa-2b, Peginterferon alfa-2a, entecavir, lamivudine, adefovir, telbivudine, tenofovir, sofosbuvir, ledipasvir, ombitasvir, paritaprevir, ritonavir, dasabuvir, grazoprevir, elbasvir, asunaprevir, daclatasvir, or beclabuvir.
25. The method of claim 19 , wherein the effective amount is 200-500 mg administered once daily, twice daily, or thrice daily.
26. The method of claim 19 , wherein the effective amount is at least 200 mg administered once daily, twice daily, or thrice daily.
27. The method of claim 19 , wherein the effective amount is at least 300 mg administered once daily, twice daily, or thrice daily.
28. The method of claim 19 , wherein the effective amount is at least 400 mg administered once daily, twice daily, or thrice daily.
29. The method of claim 19 , wherein the effective amount is at least 500 mg administered once daily, twice daily, or thrice daily.
30. The method of claim 19 , wherein clemizole, the deuterated analog of clemizole, or the clemizole metabolite is administered for greater than 2 months.
31. The method of claim 19 , wherein clemizole, the deuterated analog of clemizole, or the clemizole metabolite is administered for greater than 3 months.
32. The method of claim 19 , wherein clemizole, the deuterated analog of clemizole, or the clemizole metabolite is administered for greater than 4 months.
33. The method of claim 19 , wherein clemizole, the deuterated analog of clemizole, or the clemizole metabolite is administered for greater than 5 months.
34. The method of claim 19 , further comprising administering an effective amount of an inhibitor of CYP3A4.
35. The method of claim 19 , wherein the subject has been diagnosed with Hepatitis B infection.
36. The method of claim 19 , wherein the subject has been diagnosed with cirrhosis of the liver.
37. The method of any one of claim 1 , 7 , 18 , or 19 , wherein the subject is administered clemizole.