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, consisting of administering a therapeutically effective amount of tipifarnib to said subject, wherein said HNSCC is at an advanced stage, metastatic, relapsed or refractory.
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 , comprising determining the presence of H-Ras mutation in a sample from said subject.
4. The method of claim 3 , wherein said sample is a tumor biopsy.
5. The method of claim 3 , 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.
6. The method of claim 1 , wherein tipifarnib is administered at a dose of 1-1000 mg/kg body weight.
7. The method of claim 1 , wherein tipifarnib is administered twice a day.
8. The method of claim 1 , wherein tipifarnib is administered at a dose of 600 mg twice a day.
9. The method of claim 1 , wherein tipifarnib is administered at a dose of 900 mg twice a day.
10. The method of claim 1 , wherein tipifarnib is administered for a period of one to seven days.
11. The method of claim 1 , wherein tipifarnib is administered on days 1-7 and 15-21 of a 28-day treatment cycle.
12. The method of claim 1 , wherein tipifarnib is administered at a dose of 600 mg twice a day on days 1-7 and 15-21 of a 28-day treatment cycle.
13. 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.
14. The method of claim 1 , wherein tipifarnib is administered at a dose of 300 mg twice a day for 3 of 4 weeks in repeated 4 week cycles.