Farnesyltransferase inhibition in hematologic malignancies: The clinical experience with tipifarnib

Clinical Advances in Hematology and Oncology

Volumn 6, Issue 4, 2008, Pages 303-310

  Martinelli, Giovanni ^a   Iacobucci, Ilaria ^b   Paolini, Stefania ^b   Ottaviani, Emanuela ^b  

^a UNIVERSITY OF BOLOGNA   (Italy)

^b NONE

Author keywords

Acute myeloid leukemia; Chronic myelogenous leukemia; Farnesyltransferase inhibitor; Hematologic malignancy; Tipifarnib

Indexed keywords

CYTARABINE; ETOPOSIDE; HYDROXYUREA; IDARUBICIN; IMATINIB; PROTEIN FARNESYLTRANSFERASE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; RAS PROTEIN; TIPIFARNIB; ANTINEOPLASTIC AGENT; FARNESYL TRANS TRANSFERASE; QUINOLONE DERIVATIVE;

ACUTE GRANULOCYTIC LEUKEMIA; ANEMIA; ANTINEOPLASTIC ACTIVITY; ATAXIA; BLOOD TOXICITY; BONE MARROW SUPPRESSION; CARCINOGENESIS; CENTRAL NERVOUS SYSTEM DISEASE; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; CONFUSION; DIARRHEA; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ERUPTION; DRUG MECHANISM; DRUG SAFETY; DRUG TARGETING; DRUG TOLERABILITY; DYSARTHRIA; ENZYME INHIBITION; FATIGUE; FEBRILE NEUTROPENIA; GASTROINTESTINAL DISEASE; GASTROINTESTINAL SYMPTOM; HEMATOLOGIC MALIGNANCY; HUMAN; HYPERBILIRUBINEMIA; HYPOKALEMIA; IN VITRO STUDY; IN VIVO STUDY; INFECTION; KIDNEY DISEASE; KIDNEY DYSFUNCTION; LEG PAIN; LIVER FAILURE; LOW DRUG DOSE; METABOLIC ACIDOSIS; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; MYELODYSPLASTIC SYNDROME; MYELOFIBROSIS; MYELOID METAPLASIA; NAUSEA; NEUROTOXICITY; NEUTROPENIA; NONHODGKIN LYMPHOMA; POLYDIPSIA; REVIEW; SIDE EFFECT; SKIN DISEASE; SYNCOPE; BLOOD DISEASE; CELL DIFFERENTIATION; CELL PROLIFERATION; DRUG ANTAGONISM; DRUG EFFECT; PATHOPHYSIOLOGY; SIGNAL TRANSDUCTION;

ANTINEOPLASTIC AGENTS; CELL DIFFERENTIATION; CELL PROLIFERATION; CLINICAL TRIALS AS TOPIC; FARNESYLTRANSTRANSFERASE; HEMATOLOGIC NEOPLASMS; HUMANS; QUINOLONES; SIGNAL TRANSDUCTION;

EID: 46449100469     PISSN: 15430790     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (45)

1. Boguski MS, McCormick F. Proteins regulating Ras and its relatives. Nature. 1993;366:643-654. (Pubitemid 24036012)
2. End DW. Farnesyl protein transferase inhibitors and other therapies targeting the Ras signal transduction pathway. Invest New Drugs. 1999;17:241-258.
3. End DW, Mevellec L, Angibaud P. Farnesyl protein transferase inhibitors: molecular mechanisms and progress in the clinic. Curr Top Med Chem. [In press.]
4. Khosravi-Far R, Cox AD, Kato K, Der CJ. Protein prenylation: key to ras function and cancer intervention? Cell Growth Differ. 1992;3:461-469.
5. Rowinsky EK, Windle JJ, Von Hoff DD. Ras protein farnesyltransferase: a strategic target for anticancer therapeutic development. J Clin Oncol. 1999;17:3631-3652.
6. Reuter CWM, Morgan MA, Bergmann L. Targeting the Ras signaling pathway: a rational, mechanism-based treatment for hematologic malignancies? Blood. 2000;96:1655-1669. (Pubitemid 30661043)
7. Karp JE. Farnesyl protein transferase inhibitors as targeted therapies for hematologic malignancies. Semin Hematol. 2001;38(3 suppl 7):16-23. (Pubitemid 32845721)
8. Sebti SM, Hamilton AD. Farnesyltransferase and geranylgeranyltransferase I inhibitors in cancer therapy: important mechanistic and bench to bedside issues. Expert Opin Investig Drugs. 2000;9:2767-2782.
9. Du W, Prendergast GC. Geranylgeranylated RhoB mediates suppression of human tumor cell growth by farnesyltransferase inhibitors. Cancer Res. 1999;59:5492-5496. (Pubitemid 29526464)
10. Klippel A, Escobedo MA, Wachowicz MS, et al. Activation of phosphatidylinositol 3-kinase is sufficient for cell cycle entry and promotes cellular changes characteristic of oncogenic transformation. Mol Cell Biol. 1998;18:5699-5711. (Pubitemid 28450521)
11. Lancet JE, Karp JE. Farnesyltransferase inhibitors in hematologic malignancies: new horizons in therapy. Blood. 2003;102:3880-3889.
12. Prendergast GC, Oliff A. Farnesyltransferase inhibitors: antineoplastic properties, mechanisms of action, and clinical prospects. Semin Cancer Biol. 2000;10:443-452. (Pubitemid 32181914)
13. Harousseau JL. Farnesyltransferase inhibitors in hematologic malignancies. Blood Rev. 2007;21:173-182.
14. Harousseau JL, Lancet JE, Reiffers J, et al. A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib in patients with refractory or relapsed acute myeloid leukemia. Blood. 2007;109:5151-5156. (Pubitemid 46890529)
15. Raponi M, Harousseau JL, Lancet JE, et al. Identification of molecular predictors of response in a study of tipifarnib treatment in relapsed and refractory acute myelogenous leukemia. Clin Cancer Res. 2007;13:2254-2260. (Pubitemid 46649895)
16. Ashar HR, James L, Gray K, et al. Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules. J Biol Chem. 2000;275:30451-30457. (Pubitemid 30751364)
17. Crespo NC, Ohkanda J, Yen TJ, Hamilton AD, Sebti SM. The farnesyltransferase inhibitor, FTI-2153, blocks bipolar spindle formation and chromosome alignment and causes prometaphase accumulation during mitosis of human lung cancer cells. J Biol Chem. 2001;276:16161-16167. (Pubitemid 37391656)
18. Zujewski J, Horak ID, Bol CJ, et al. Phase I and pharmacokinetic study of farnesyl protein transferase inhibitor R115777 in advanced cancer. J Clin Oncol. 2000;18:927-941. (Pubitemid 30106625)
19. Sebti SM, Adjei AA. Farnesyltransferase inhibitors. Semin Oncol. 2004;31(1 suppl 1):28-39.
20. Karp JE, Lancet JE, Kaufmann SH, et al. Clinical and biologic activity of the farnesyltransferase inhibitor R115777 in adults with refractory and relapsed acute leukemias: a phase 1 clinical-laboratory correlative trial. Blood. 2001;97:3361-3369.
21. Kirschbaum M, Selwyn Stein A, Tuscano J, et al. A phase I study of the farnesyltransferase inhibitor tipifarnib in a week-on week-off dose schedule in acute myelogenous leukemia. Blood. 2006;108:551a. Abstract 1948.
22. Lancet JE, Gojo I, Gotlib J, et al. A phase 2 study of the farnesyltransferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myelogenous leukemia. Blood. 2007;109:1387-1394. (Pubitemid 46242109)
23. Karp JE, Smith BD, Gojo I, et al. Phase II trial of the oral farnseyltransferase inhibitor tipifarnib as maintenance therapy in first complete remission in adults with acute myelogenous leukemia and poor risk features. Clin Cancer Res. [In press.]
24. Kurzrock R, Kantarjian HM, Cortes JE, et al. Farnesyltransferase inhibitor R115777 in myelodysplastic syndrome: clinical and biologic activities in the phase 1 setting. Blood. 2003;102:4527-4534. (Pubitemid 37494120)
25. Kurzrock R, Verstovsek S, Wright JJ, et al. Phase I study using alternate week administration of the farnesyl transferase inhibitor R115777 (Zarnestra) in patients with myelodysplastic syndrome. Blood. 2004;104(pt 1):402a. Abstract 1436.
26. Kurzrock R, Albitar M, Cortes JE, et al. Phase II study of R115777, a farnesyl transferase inhibitor, in myelodysplastic syndrome. J Clin Oncol. 2004;22:1287-1292. (Pubitemid 41079843)
27. Fenaux P, Raza A, Mufti GJ, et al. A multicenter phase 2 study of the farnesyltransferase inhibitor tipifarnib in intermediate- to high-risk myelodysplastic syndrome. Blood. 2007;109:4158-4163. (Pubitemid 46743377)
28. Shah NP. Loss of response to imatinib: mechanisms and management. Hematology Am Soc Hematol Educ Program. 2005;183-187.
29. Hoover RR, Mahon FX, Melo JV, Daley GQ. Overcoming STI571 resistance with the farnesyl transferase inhibitor SCH66336. Blood. 2002;100:1068-1071.
30. Nakajima A, Tauchi T, Ohyashiki K. ABL-specific tyrosine kinase inhibitor, STI571 in vitro, affects Ph-positive acute lymphoblastic leukemia and chronic myelogenous leukemia in blastic crisis. Leukemia. 2001;15:989-990. (Pubitemid 32529902)
31. Cortes J, Albitar M, Thomas D, et al. Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematologic malignancies. Blood. 2003;101:1692-1697. (Pubitemid 36237561)
32. Beaupre DM, Cepero E, Obeng EA, Boise LH, Lichtenheld MG. R115777 induces Ras-independent apoptosis of myeloma cells via multiple intrinsic pathways. Mol Cancer Ther. 2004;3:179-186. (Pubitemid 39193692)
33. Bolick SC, Landowski TH, Boulware D, et al. The farnesyl transferase inhibitor, FTI-277, inhibits growth and induces apoptosis in drug-resistant myeloma tumor cells. Leukemia. 2003;17:451-457. (Pubitemid 36266924)
34. Mesa RA, Tefferi A, Gray LA, Reeder T, Schroeder G, Kaufmann SH. In vitro antiproliferative activity of the farnesyltransferase inhibitor R115777 in hematopoietic progenitors from patients with myelofibrosis with myeloid metaplasia. Leukemia. 2003;17:849-855. (Pubitemid 36626310)
35. Alsina M, Fonseca R, Wilson EF, et al. Farnesyltransferase inhibitor tipifarnib is well tolerated, induces stabilization of disease, and inhibits farnesylation and oncogenic/tumor survival pathways in patients with advanced multiple myeloma. Blood. 2004;103:3271-3277. (Pubitemid 38525650)
36. Mesa RA, Camoriano JK, Geyer SM, et al. A phase 2 consortium (P2C) trial of R115777 (tipifarnib) in myelofibrosis with myeloid metaplasia. Blood. 2004;104(pt 1):422a. Abstract 1509.
37. Witzig TE, Maurer MJ, Johnston PB, et al. Oral tipifarnib (R115777) has single agent anti-tumor activity in patients with relapsed aggressive non-Hodgkin lymphoma (NHL): results of a phase II trial in the University of Iowa/Mayo Clinic Lymphoma SPORE (CA97274). Blood. 2006;108. Abstract 530.
38. Cortes J, Garcia-Manero G, O'Brien S, et al. A phase I study of tipifarnib in combination with imatinib mesylate (IM) for patients (Pts) with chronic myeloid leukemia (CML) in chronic phase (CP) who failed IM therapy. Blood. 2004;104(pt 1):176. Abstract 1011.
39. Gotlib J, Mauro M, O'Dwyer ME, et al. Tipifarnib (ZARNESTRA) and Imatinib (GLEEVEC) combination therapy in patients with advanced chronic myelogenous leukemia (CML): preliminary results of a phase I study. Blood. 2003;102:909a. Abstract 3384.
40. Karp JE, Feldman EJ, Morris L. Active oral regimen for elderly adults with newly diagnosed acute myelogenous leukemia (AML): phase I trial of oral tipifarnib (T) combined with oral etoposide (E) for adults age 70 who are not candidates for traditional cytotoxic chemotherapy (TCC). Blood. 2006;106. Abstract 426.
41. Alvarez RH, Kantarjian H, Garcia-Manero G, et al. Farnesyl transferase inhibitor (tipifarnib, Zarnestra; Z) in combination with standard chemotherapy with idarubicin (IDA) and cytarabine (ara-C) for patients (pts) with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Blood. 2006;106:565a-566a. Abstract 1999.
42. Cortes JE, Feldman EJ, Douer D, Raza A, Fruchtman S. Phase I evaluation of tipifarnib in combination with low-dose Ara-C (LDAC) in high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML): interim results. J Clin Oncol. 2007;25:Abstract 14014.
43. Raponi M, Harousseau JL, Lancet JE, et al. Identification of molecular predictors of response in a study of tipifarnib treatment in relapsed and refractory acute myelogenous leukemia. Clin Cancer Res. 2007;13:2254-2260. (Pubitemid 46649895)
44. Raponi M, Lancet JE, Fan H, et al. A two gene classifier for predicting response to the farnesyltansferase inhibitor tipifarnib in acute myeloid leukemia. Blood. 2008;111:2589-2596.
45. Goemans BF, Zwaan CM, Harlow A, et al. In vitro profiling of the sensitivity of pediatric leukemia cells to tipifarnib: identification of T-cell ALL and FAB M5 AML as the most sensitive subsets. Blood. 2005;106:3532-3537. (Pubitemid 41609190)