Methods of treating cancer with farnesyltransferase inhibitors
The present invention relates to the field of cancer therapy. Specifically, provided are methods of treating cancer, for example, peripheral T-cell lymphoma (“PTCL”), with a farnesyltransferase inhibitor (FTI) that include determining whether the subject is likely to be responsive to the FTI treatment based on gene expression characteristics.
1. A method of treating an angioimmunoblastic T-cell lymphoma (AITL) in a subject, comprising administering a therapeutically effective amount of tipifarnib to the subject.
2. The method of claim 1 , wherein the AITL is relapsed or refractory AITL.
3. The method of claim 1 , wherein tipifarnib is selectively administered to the subject on the basis that the subject has a tumor of AITL histology.
4. The method of claim 3 , wherein the AITL histology is characterized by a tumor cell component.
5. The method of claim 4 , wherein the tumor cell component comprises polymorphous medium-sized neoplastic cells derived from follicular helper T cells.
6. The method of claim 3 , wherein the AITL histology is characterized by a non-tumor cell component.
7. The method of claim 6 , wherein the non-tumor cell component comprises prominent arborizing blood vessels.
8. The method of claim 7 , wherein the non-tumor cell component comprises proliferation of follicular dendritic cells.
9. The method of claim 8 , wherein the non-tumor cell component comprises scattered EBV positive B-cell blasts.
10. The method of claim 1 , wherein the subject having AITL has been diagnosed with AITL.
11. The method of claim 10 , wherein diagnosis with AITL comprises visualization of a non-tumor component.
12. The method of claim 10 , wherein diagnosis with AITL comprises visualization of proliferation of endothelial venules.
13. The method of claim 10 , wherein diagnosis with AITL comprises detecting the presence of one or more of the following tumor markers: CXCL13, CD10, PD1, and BCL6.
14. The method of claim 1 , wherein tipifarnib is administered orally, parenterally, rectally, or topically.
15. The method of claim 1 , wherein tipifarnib is administered at a dose of 0.05-500 mg/kg body weight.
16. The method of claim 1 , wherein tipifarnib is administered twice a day.
17. The method of claim 1 , wherein tipifarnib is administered at a dose of 200-1200 mg twice a day.
18. The method of claim 17 , wherein the tipifarnib is administered at a dose of 100 mg, 200 mg, 300 mg, 400 mg, 600 mg, 900 mg or 1200 mg twice a day.
19. The method of claim 1 , wherein the tipifarnib is administered on days 1-7 and 15-21 of a 28-day treatment cycle.
20. The method of claim 1 , wherein the tipifarnib is administered on days 1-21 of a 28-day treatment cycle.
21. The method of claim 1 , wherein the tipifarnib is administered on days 1-7 of a 28-day treatment cycle.
22. The method of claim 21 , wherein tipifarnib is administered at a dose of 900 mg twice a day.
23. The method of claim 21 , wherein tipifarnib is administered at a dose of 600 mg twice a day.
24. The method of claim 21 , wherein tipifarnib is administered at a dose of 400 mg twice a day.
25. The method of claim 21 , wherein tipifarnib is administered at a dose of 300 mg twice a day.
26. The method of claim 21 , wherein tipifarnib is administered at a dose of 200 mg twice a day.
27. The method of claim 1 , wherein tipifarnib is administered before, during, or after radiation.
28. The method of claim 1 , further comprising administering a therapeutically effective amount of a second active agent or a support care therapy.
29. The method of claim 26 , wherein the second active agent is a histone deacetylase, an antifolate, or chemotherapy.
30. The method of claim 1 , that consists of administering a therapeutically effective amount of tipifarnib to the subject.