Treatment of cancer with specific RXR agonists
A method of treating cancer is disclosed comprising administering to a patient in need of such treatment a RXR agonist at a level below the RAR activating threshold and at or above the RXR effective dose.
1. A method of treating colorectal cancer comprising administering to a patient in need of such treatment a retinoid X receptor (RXR) agonist at a dose below its Retinoic Acid Receptor (RAR) activating threshold and at or above its RXR effective dose, the RXR agonist has a chemical structure
where R is H, lower alkyl or 1 to 6 carbons, or a pharmaceutically acceptable salt of the compound, and the dose of the RXR agonist is from about 1 to about 20 mg/m 2 /day.
2. The method according to claim 1 , wherein the RAR activating threshold and the RXR effective dose for the patient is determined by dosing the patient with increasing concentrations of a RXR agonist to until the RXR effective dose and the RAR activating threshold are reached.
3. The method according to claim 2 , wherein the RXR effective dose is determined by measuring a reduction of the patient's TSH levels or at least one RAR biomarker expressed by the patient.
4. The method according to claim 3 , wherein the RAR biomarker is selected from the group consisting of CYP26 level, CRBPI level and combinations thereof.
5. The method according to claim 1 , further comprising measuring the patient's C max of the RXR agonist, and adjusting the dose to maintain the patient's C max at an optimal level.
6. The method according to claim 1 , further comprising treating the patient with at least one other agent selected from the group consisting of anti-cancer agents, triglyceride lowering agents and TSH modulating agents.
7. The method according to claim 6 , wherein the anti-cancer agent is selected from the group consisting of a platinum-based compounds, cytotoxic drugs, and mixtures thereof.
8. The method according to claim 1 , wherein the dose of the RXR agonist is from about 1 to about 10 mg/m 2 /day.
9. The method according to claim 1 , wherein the dose of the RXR agonist is from about 10 to about 20 mg/m 2 /day.
10. The method according to claim 1 , wherein the RXR agonist is 3,7-di methyl-6(S),7(S)-methano,7-[1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphth-7-yl]2(E),4(E) heptadienoic acid.
11. The method according to claim 1 , wherein the colorectal cancer is colon cancer.
12. The method according to claim 1 , wherein the colorectal cancer is rectal cancer.