Methods of treating cancer patients with farnesyltransferase inhibitors
The present invention relates to the field of molecular biology and cancer biology. Specifically, the present invention relates to methods of treating a subject with a farnesyltransferase inhibitor (FTI) that include determining whether the subject is likely to be responsive to the FTI treatment based on genotyping and expression profiling of certain immunological genes and RAS mutation status in the subject.
1. A method of treating a H-Ras mutant head and neck squamous cell carcinoma (HNSCC) in a subject, comprising administering a therapeutically effective amount of tipifarnib to said subject, wherein said HNSCC is at an advanced stage, metastatic, relapsed or refractory and wherein said HNSCC is human papillomavirus (HPV)-negative.
2. The method of claim 1 , wherein the H-Ras mutation of said subject comprises an amino acid substitution at a codon selected from the group consisting of G12, G13, and Q61.
3. The method of claim 1 , wherein said H-Ras mutation of said subject comprises an amino acid substitution at codon G12.
4. The method of claim 1 , wherein said H-Ras mutation of said subject comprises an amino acid substitution at codon G13.
5. The method of claim 1 , wherein said H-Ras mutation of said subject comprises an amino acid substitution at codon Q61.
6. The method of claim 1 , comprising determining the presence of H-Ras mutation in a sample from said subject.
7. The method of claim 6 , wherein said sample is a tissue biopsy.
8. The method of claim 6 , wherein said sample is a tumor biopsy.
9. The method of claim 6 , wherein said H-Ras mutation is determined by a method selected from the group consisting of sequencing, Polymerase Chain Reaction (PCR), DNA microarray, Mass Spectrometry (MS), Single Nucleotide Polymorphism (SNP) assay, denaturing high-performance liquid chromatography (DHPLC), and Restriction Fragment Length Polymorphism (RFLP) assay.
10. The method of claim 1 , wherein tipifarnib is administered at a dose of 1-1000 mg/kg body weight.
11. The method of claim 1 , wherein tipifarnib is administered twice a day.
12. The method of claim 1 , wherein tipifarnib is administered at a dose of 600 mg twice a day.
13. The method of claim 1 , wherein tipifarnib is administered at a dose of 900 mg twice a day.
14. The method of claim 1 , wherein tipifarnib is administered for a period of one to seven days.
15. The method of claim 1 , wherein tipifarnib is administered on days 1-7 and 15-21 of a 28-day treatment cycle.
16. The method of claim 15 , wherein tipifarnib is administered for at least 3 cycles.
17. The method of claim 15 , wherein tipifarnib is administered for at least 6 cycles.
18. The method of claim 15 , wherein said treatment cycle continues for up to 12 months.
19. The method of claim 1 , wherein tipifarnib is administered at a dose of 900 mg twice a day on days 1-7 and 15-21 of a 28-day treatment cycle.
20. The method of claim 1 , wherein the tipifarnib is administered before, during, or after irradiation.
21. The method of claim 1 , further comprising administering a therapeutically effective amount of a second active agent or a support care therapy.
22. The method of claim 21 , wherein said second active agent is selected from the group consisting of a DNA-hypomethylating agent, a therapeutic antibody that specifically binds to a cancer antigen, a hematopoietic growth factor, a cytokine, an antibiotic, a cox-2 inhibitor, an immunomodulatory agent, an anti-thymocyte globulin, an immunosuppressive agent, and a corticosteroid or a pharmacological derivative thereof.
23. The method of claim 21 , wherein said second active agent is an anti-PD1 antibody or an anti-PDL1 antibody.