Tipifarnib: farnesyl transferase inhibition at a crossroads

References

• End DW, Smets G, Todd AV et al. Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res. 91, 131–137 (2001).
   Google Scholar
• Gibbs JB, Oliff A. The potential of farnesyltransferase inhibitors as cancer chemotherapeutics. Ann. Rev. Pharmacol. Toxicol. 37, 143–166 (1997).
   PubMed Web of Science ®Google Scholar
• Zhang FL, Casey PJ. Protein prenylation: molecular mechanisms and functional consequences. Ann. Rev. Biochem. 65, 241–269 (1996).
   PubMed Web of Science ®Google Scholar
• Sinensky M. Recent advances in the study of prenylated proteins. Biochem. Biophys. Acta 1484, 93–106 (2000).
   PubMed Web of Science ®Google Scholar
• Beaupre DM, Kurzrock R. RAS and leukemia: from basic mechanisms to gene-directed therapy. J. Clin. Oncol. 17, 1071–1079 (1999).
   PubMed Web of Science ®Google Scholar
• Rowinsky EK, Windle JJ, Von Hoff DD. Ras protein farnesyltransferase: a strategic target for anticancer therapeutic development. J. Clin. Oncol. 17, 3631–3652 (1999).
   PubMed Web of Science ®Google Scholar
• Adjei AA. Blocking oncogenic Ras signaling for cancer therapy. J. Natl Cancer Inst. 93, 1062–1074 (2001).
   PubMed Web of Science ®Google Scholar
• Pendergast AM, Quilliam LA, Cripe LD et al. BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein. Cell 75, 175–185 (1993).
   PubMed Web of Science ®Google Scholar
• Karp JE, Kaufmann, SH, Adjei AA, Lancet JE, Wright, JJ, End DW. Current status of clinical trials of farnesyltransferase inhibitors. Curr. Opin. Oncol. 13, 470–476 (2001).
   PubMed Web of Science ®Google Scholar
• Gelb MH, Scholten JD, Sebolt-Leopold JS. Protein prenylation: from discovery to prospects for cancer treatment. Curr. Opin. Chem. Biol. 2, 40–48 (1998).
   PubMed Web of Science ®Google Scholar
• Sebti S, Hamilton AD. Inhibitors of prenyl transferases. Curr. Opin. Oncol. 9, 557–561 (1997).
   PubMedGoogle Scholar
• 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. 18, 927–941 (2000).
   PubMed Web of Science ®Google Scholar
• 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 97, 3361–3369 (2001).
   PubMed Web of Science ®Google Scholar
• Punt CJ, van Maanen L, Bol CJ, Seifert WF, Wagener DJ. Phase I and pharmacokinetic study of the orally administered farnesyl transferase inhibitor R115777 in patients with advanced solid tumors. Anticancer Drugs 12, 193–197 (2001).
   PubMed Web of Science ®Google Scholar
• Schellens J, de Klerk G. Phase I and pharmacologic study with the novel farnesyl transferase inhibitor (FTI) R115777. Proc. Am. Soc. Clin. Oncol. 19, (2000) (Abstract 715).
   Google Scholar
• Rao S, Cunningham D, de Gramont A et al. Phase III double-blind placebo-controlled study of farnesyl transferase inhibitor R115777 in patients with refractory advanced colorectal cancer. J. Clin. Oncol. 22, 3950–3957 (2004).
   PubMed Web of Science ®Google Scholar
• Van Custem E, van de Velde H, Karasek, P. Phase III trial of gemcitibine plus tipifarnib compared to gemcitibine plus placebo in advanced pancreatic cancer. J. Clin. Oncol. 22, 1430–1438 (2004).
   PubMedGoogle Scholar
• Lebowitz PF, Eng-Wong J, Widemann, BC. A Phase I trial and pharmacokinetic study of tipifarnib, a farnesyltransferase inhibitor, and tamoxifen in metastatic breast cancer. Clin. Cancer Res. 11, 1247–1252 (2005).
   Google Scholar
• Miyoshi T, Nagai T, Ohmine K et al. Relative importance of apoptosis and cell cycle blockage in the synergistic effect of combined R115777 and imatinib treatment in BCR/ABL-positive cell lines. Biochem. Pharmacol. 69, 1585–1594 (2005).
   Google Scholar
• Caraglia M, Giuberti G, Marra M et al. Docetaxel induces p53-dependent apoptosis and synergizes with farnesyl transferase inhibitor r115777 in human epithelial cancer cells. Front. Biosci. 10, 2566–2575 (2005).
   PubMed Web of Science ®Google Scholar
• Cohen SJ, Gallo J, Lewis NL et al. Phase I and pharmacokinetic study of the farnesyltransferase inhibitor R115777 in combination with irinotecan in patients with advanced cancer. Cancer Chemother. Pharmacol. 53, 513–518 (2004).
   PubMed Web of Science ®Google Scholar
• Head J, Johnston SR. New targets for therapy in breast cancer: farnesyltransferase inhibitors. Breast Cancer Res. 6, 262–268 (2004).
   Google Scholar
• Skrazt S, Bowden C, End D. Interaction of the farnesyl protein transferase inhibitor R115777 with cytotoxic chemotherapeutics in vitro and in vivo (abstract). Proc. Am. Assoc. Cancer Res. 40, 523 (1999) (Abstract 3447) .
   Google Scholar
• Johnston SR, Hickish T, Ellis P et al. Phase II study of the efficacy and tolerability of two dosing regimens of the farnesyl transferase inhibitor, R115777, in advanced breast cancer. J. Clin. Oncol. 21, 2492–2499 (2003).
   PubMed Web of Science ®Google Scholar
• End DW, Smets G, Todd AV et al. Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res. 61, 131–137 (2001).
   PubMed Web of Science ®Google Scholar
• Adjei AA, Mauer A, Bruzek L et al. Phase II study of the farnesyl transferase inhibitor R115777 in patients with advanced non-small-cell lung cancer. J. Clin. Oncol. 21, 1760–1766 (2003).
   PubMed Web of Science ®Google Scholar
• Heymach JV, Johnson DH, Khuri, FR et al. Phase II study of the farnesyl transferase inhibitor R115777 in patients with sensitive relapse small-cell lung cancer. Ann. Oncol. 15, 1187–1193 (2004).
   PubMed Web of Science ®Google Scholar
• Macdonald JS, McCoy S, Whitehead RP et al. A Phase II study of farnesyl transferase inhibitor R115777 in pancreatic cancer: a Southwest Oncology Group (SWOG 9924) study. Invest. New Drugs 23, 485–487 (2005).
   PubMed Web of Science ®Google Scholar
• Rosenberg JE, von der Maase H, Seigne JD et al. A Phase II trial of R115777, an oral farnesyl transferase inhibitor, in patients with advanced urothelial tract transitional cell carcinoma. Cancer 103, 2035–2041 (2005).
   PubMed Web of Science ®Google Scholar
• Lustig RA, Mikkelesen T, Lesser G et al. New approaches to brain tumor therapy consortium pre-radiation R115777 in patients with newly diagnosed glioblastoma multiforme and residual enhancing disease. J. Clin. Oncol. (Meeting Abstracts), 23, 1518 (2005).
   Google Scholar
• Patnaik A, Mita AC, Izbicka E et al. A Phase I, pharmacokinetic (PK), and pharmacodynamic (PD) study of the farnesyl transferase inhibitor (FTI) R115777 in combination with weekly paclitaxel in patients (pts) with advanced solid cancers. J. Clin. Oncol. (Meeting Abstracts), 22, 3136 (2004).
   Google Scholar
• Ma CX, Croghan G, Reid J et al. A Phase I trial of the combination of erlotinib and tipifarnib in patients with advanced solid tumors. J. Clin. Oncol. (Meeting Abstracts), 23, 3000 (2005).
   Google Scholar
• Lancet JE, Karp JE. Farnesyl transferase inhibitors in myeloid malignancies. Blood Rev. 17, 123–129 (2003).
   PubMed Web of Science ®Google Scholar
• Bos, JL, Verlaan-de Vries M, van der Eb et al. Mutations in N-ras predominate in acute myeloid leukemia. Blood 69, 1237–1241 (1987).
   PubMed Web of Science ®Google Scholar
• Wright J, Blatner GL, Cheson BD. Clinical trials referral resource. Clinical trials with the farnesyl transferase inhibitor R115777. Oncology (Huntingt), 13, 1527, 1530, 1533 (1999).
   Google Scholar
• Lancet JE, Gotlib J, Gojo I et al. Tipifarnib (ZARNESTRATM in previously untreated poor-risk AML of the elderly: updated results of a multicenter Phase II trial. ASH Annual Meeting Abstracts 104, 874 (2004).
   Google Scholar
• Harousseau JL, Reiffers, J, Lowenberg B. R115777 in patients with relapsed and refractory acute myelogenous leukemia (AML): results of a mutlicenter Phase II study. Blood 102, (2003) (Abstract 614).
   Google Scholar
• Kurzrock R, Kantarjian HM, Cortes JE et al. Farnesyltransferase inhibitor R115777 in myelodysplastic syndrome: clinical and biologic activities in the Phase I setting. Blood 102, 4527–4534 (2003).
   PubMed Web of Science ®Google Scholar
• Kurzrock R, Albitar M, Cortes JE et al. Phase II study of R115777, a farnesyl transferase inhibitor, in myelodysplastic syndrome. J. Clin. Oncol. 22, 1287–1292 (2004).
   PubMed Web of Science ®Google Scholar
• Kurzrock R, Fenaux P, Raza A et al. High-risk myelodysplastic syndrome (MDS): first results of International Phase II study with oral Farnesyltransferase inhibitor R115777 (ZARNESTRATM). ASH Annual Meeting Abstracts 104, 68 (2004).
   Google Scholar
• Kurzrock R, Verstovsek S, Wright JJ et al. Phase I study using alternate week administration of the farnesyl transferase inhibitor R115777 (zarnestratm) in patients with myelodysplastic syndrome. ASH Annual Meeting Abstracts 104, 1436 (2004).
   Google Scholar
• Tefferi A. Myelofibrosis with myeloid metaplasia. N. Engl. J. Med. 342, 1255–1265 (2000).
   PubMed Web of Science ®Google Scholar
• 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 17, 849–855 (2003).
   PubMed Web of Science ®Google Scholar
• Mesa RA, Camoriano JK, Geyer SM et al. A Phase 2 Consortium (P2C) Trial of R115777 (Tipifarnib) in Myelofibrosis with Myeloid Metaplasia. Blood 104, (2004) (Abstract 1509).
   Google Scholar
• Gotlib J, Loh M, Lancet JE et al. Phase I/II study of tipifarnib (Zarnestra, farnesyltransferase inhibitor (FTI) R115777) in patients with myeloproliferative disorders (MPDs): Interim Results. Blood 102, (2003) (Abstract 3425).
   Google Scholar
• Druker BJ, Talpaz M, Resta DJ et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344, 1031–1037 (2001).
   PubMed Web of Science ®Google Scholar
• Cortes J, Albitar M, Thomas D et al. Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematologic malignancies. Blood 101, 1692–1697 (2003).
   PubMed Web of Science ®Google Scholar
• Gotlib J, Mauro MJ, O'Dwyer M et al. Tipifarnib and Imatinib Combination Therapy in Patients with Advanced Chronic Myelogenous Leukemia (CML): preliminary results of a Phase I study. Blood 102, (2003) (Abstract 3384).
   Google Scholar
• Golemovic M, Giles FJ, Beran M et al. AMN107, a novel aminopyrimidine inhibitor of bcr-abl, has pre-clinical activity against imatinib mesylate-resistant chronic myeloid leukemia (CML). Blood 104, (2004) (Abstract 1983).
   Google Scholar
• Sawyers CL, Shah NP, Kantarjian HM et al. Hematologic and cytogenetic responses in imatinib-resistant chronic phase chronic myeloid leukemia patients treated with the dual src/abl kinase inhibitor BMS-354825: results from a Phase I dose escalation Study. Blood 104 (2004) (Abstract 1).
   Google Scholar
• 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 103, 3271–3277 (2004).
   PubMed Web of Science ®Google Scholar
• List A, Kurtin SE, Glinsmann-Gibson BJ et al. High erythropoietic remitting activity of the immunomodulatory thalidomide analog CC5013, in patients with myelodysplastic syndrome (MDS). Blood 100, (2003) (Abstract 353).
   Google Scholar
• Van Cutsem E, van de Velde H, Karasek P et al. Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J. Clin. Oncol. 22, 1430–1438 (2004).
   PubMed Web of Science ®Google Scholar
• Cortes J, Garcia-Moreno G, O'Brien S et al. Phase I study of imatinib and tipifarnib in patients with chronic myeloid leukemia in chronic phase refractory to imatinib. Blood 102, (2003) (Abstract 3383).
   Google Scholar