Phase I and pharmacokinetic study of farnesyl protein transferase inhibitor R115777 in advanced cancer

Journal of Clinical Oncology

Volumn 18, Issue 4, 2000, Pages 927-941

  Zujewski, J ^a   Horak, I D ^a   Bol, C J ^a   Woestenborghs, R ^a   Bowden, C ^a   End, D W ^a   Piotrovsky, V K ^a   Chiao, J ^a   Belly, R T ^a   Todd, A ^a   Kopp, W C ^a   Kohler, D R ^a   Chow, C ^a   Noone, M ^a   Hakim, F T ^a   Larkin, G ^a   Gress, R E ^a   Nussenblatt, R B ^a   Kremer, A B ^a   Cowan, K H ^a  

^a NATIONAL EYE INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; PROTEIN FARNESYLTRANSFERASE INHIBITOR; TIPIFARNIB;

ADULT; ADVANCED CANCER; AGED; ARTICLE; BLOOD TOXICITY; CARDIOVASCULAR DISEASE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG EXCRETION; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; FEMALE; GASTROINTESTINAL SYMPTOM; HEADACHE; HUMAN; MALE; NEUROPATHY; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL;

EID: 18544412314     PISSN: 0732183X     EISSN: None     Source Type: Journal    
DOI: 10.1200/jco.2000.18.4.927     Document Type: Article

References (67)

1. Barbacid M: ras genes. Annu Rev Biochem 56:779-827, 1987
2. Grunewald K, Lyons J, Frohlich A, et al: High frequency of Ki-ras codon 12 mutations in pancreatic adenocarcinomas. Int J Cancer 43:1037-1041, 1989
3. Forrester K, Almoguera C, Han K, et al: Detection of high incidence of K-ras oncogenes during human colon tumorigenesis. Nature 327:298-303, 1987
4. Vogelstein B, Fearon ER, Hamilton SR, et al: Genetic alterations during colorectal-tumor development. N Engl J Med 319:525-532, 1988
5. Reynolds SH, Anna CK, Brown KC, et al: Activated protooncogenes in human lung tumors from smokers. Proc Natl Acad Sci USA 88:1085-1089, 1991
6. Knowles MA, Williamson M: Mutation of H-ras is infrequent in bladder cancer: Confirmation by single-strand conformation polymorphism analysis, designed restriction fragment length polymorphisms, and direct sequencing. Cancer Res 53:133-139, 1993
7. Almoguera C, Shibata D, Forrester K, et al: Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53:549-554, 1988
8. Bos JL, Fearon ER, Hamilton SR, et al: Prevalence of ras gene mutations in human colorectal cancers. Nature 327:293-297, 1987
9. Mills NE, Fishman CL, Rom WN, et al: Increased prevalence of K-ras oncogene mutations in lung adenocarcinoma. Cancer Res 55: 1444-1447, 1995
10. Bos JL: ras oncogenes in human cancer: A review. Cancer Kes 49:4682-4689, 1989 [published erratum appears in Cancer Res 50: 1352, 1990.
11. Moriyama N, Umeda T, Akaza H, et al: Expression of ras p21 oncogene product on human bladder tumors. Urol Int 44:260-263, 1989
12. Clark GJ, Der CJ: Aberrant function of the Ras signal transduction pathway in human breast cancer. Breast Cancer Res Treat 35:133-144, 1995
13. Janes PW, Daly RJ, deFazio A, et al: Activation of the Ras signalling pathway in human breast cancer cells overexpressing erbB-2. Oncogene 9:3601-3608, 1994
14. Patton SE, Martin ML, Nelsen LL, et al: Activation of the ras-mitogen-activated protein kinase pathway and phosphorylation of ets-2 at position threonine 72 in human ovarian cancer cell lines. Cancer Res 58:22-53-2259, 1998
15. Feldkamp M, Lau N, Guha A: Astrocytomas are growth-inhibited by farnesyl transferase inhibitors through a combination of anti-proliferative and antiangiogenic activities. Proc Am Assoc Cancer Res 39:318, 1998 (abstr)
16. Guha A, Feldkamp MM, Lau N, et al: Proliferation of human malignant astrocytomas is dependent on Ras activation. Oncogene 15:2755-2765, 1997
17. Kato K, Der CJ, Buss JE: Prenoids and palmitate: Lipids that control the biological activity of Ras proteins. Semin Cancer Biol 3:179-188, 1992
18. Casey PJ, Solski PA, Der CJ, et al: p21ras is modified by a farnesyl isoprenoid. Proc Natl Acad Sci USA 86:8323-8327, 1989
19. Der CJ, Cox AD: Isoprenoid modification and plasma membrane association: Critical factors for ras oncogenicity. Cancer Cells 3:331-340, 1991
20. Jackson JH, Cochrane CG, Bourne JR, et al: Farnesol modification of Kirsten-ras exon 4B protein is essential for transformation. Proc Natl Acad Sci USA 87:3042-3046, 1990
21. Reiss Y, Goldstein JL, Seabra MC, et al: Inhibition of purified P21ras farnesyl:protein transferase by Cys-AAX tetrapeptides. Cell 62:81-88, 1990
22. Gutierrez L, Magee AI, Marshall CJ, et al: Post-translational processing of p21ras is two-step and involves carboxyl-methylation and carboxy-terminal proteolysis. EMBO J 8:1093-1098, 1989
23. Kato K, Cox AD, Hisaka MM, et al: Isoprenoid addition to Ras protein is the critical modification for its membrane association and transforming activity. Proc Natl Acad Sci USA 89:6403-6407, 1992
24. Kohl NE, Mosser SD, deSolms SJ, et al: Selective inhibition of ras-dependent transformation by a farnesyltransferase inhibitor. Science 260:1934-1937, 1993 (see comments)
25. James GL, Goldstein JL, Brown MS, et al: Benzodiazepine peptidomimetics: Potent inhibitors of Ras farnesylation in animal cells. Science 260:1937-1942, 1993 (see comments)
26. Garcia AM, Rowell C, Ackermann K, et al: Peptidomimetic inhibitors of Ras farnesylation and function in whole cells. J Biol Chem 268:18415-18418, 1993
27. Ward R, Hawkins N, O'Grady R, et al: Restriction endonuclease-mediated selective polymerase chain reaction: A novel assay for the detection of K-ras mutations in clinical samples. Am J Pathol 153:373-379, 1998
28. Todd AV, Applegate TL, Fuery CJ, et al: Farnesyl transferase inhibitor (FTI): Effect of ras activation. Proc Am Assoc Cancer Res 39:317, 1998 (abstr)
29. Sepp-Lorenzino L, Ma Z, Rands E, et al: A peptidomimetic inhibitor of farnesyl:protein transferase blocks the anchorage-dependent and -independent growth of human tumor cell lines. Cancer Res 55:5302-5309, 1995
30. Smets G, Xhonneux B, Cornelissen F, et al: R115777, a selective farnesyl protein transferase inhibitor (FTI), induces anti-angiogenic, apoptotic and anti-proliferative activity in CAPAN-2 and LoVo tumor xenografts. Proc Am Assoc Cancer Res 39:318, 1998 (abstr)
31. Kohl NE, Wilson FR, Mosser SD, et al: Protein farnesyltransferase inhibitors block the growth of ras-dependent tumors in nude mice. Proc Natl Acad Sci USA 91:9141-9145, 1994
32. Kohl NE, Omer CA, Conner MW, et al: Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice. Nat Med 1:792-797, 1995 (see comments)
33. Mangues R, Corral T, Kohl NE, et al: Antitumor effect of a farnesyl protein transferase inhibitor in mammary and lymphoid tumors overexpressing N-ras in transgenic mice. Cancer Res 58:1253-1259, 1998
34. Sun J, Qian Y, Hamilton AD, et al: Ras CAAX peptidomimetic FTI 276 selectively blocks tumor growth in nude mice of a human lung carcinoma with K-Ras mutation and p53 deletion. Cancer Res 55:4243-4247, 1995
35. James GL, Goldstein JL, Brown MS: Polylysine and CVIM sequences of K-RasB dictate specificity of prenylation and confer resistance to benzodiazepine peptidomimetic in vitro. J Biol Chem 270:6221-6226, 1995
36. Yokoyama K, McGeady P, Gelb MH: Mammalian protein geranylgeranyltransferase-I: Substrate specificity, kinetic mechanism, metal requirements, and affinity labeling. Biochemistry 34:1344-1354, 1995 (published erratum appears in Biochemistry 34:14270), 1995
37. Whyte DB, Kirschmeier P, Hockenberry TN, et al: K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors. J Biol Chem 272:14459-14464, 1997
38. Rowell CA, Kowalczyk JJ, Lewis MD, et al: Direct demonstration of geranylgeranylation and farnesylation of Ki-Ras in vivo. J Biol Chem 272:14093-14097, 1997
39. Liu M, Bryant MS, Chen J, et al: Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. Cancer Res 58:4947-4956, 1998
40. End D, Skrzat S, Devine A, et al: R115777, a novel imidazole farnesyl protein transferase inhibitor (FTI): Biochemical and cellular effects in H-ras and K-ras dominant systems. Proc Am Assoc Cancer Res 39:270, 1998
41. Armstrong SA, Hannah VC, Goldstein JL, et al: CAAX geranylgeranyl transferase transfers farnesyl as efficiently as geranylgeranyl to RhoB. J Biol Chem 270:7864-7868, 1995
42. Lebowitz PF, Casey PJ, Prendergast GC, et al: Farnesyltransferase inhibitors alter the prenylation and growth-stimulating function of RhoB. J Biol Chem 272:15591-15594, 1997
43. Tapon N, Hall A: Rho, Rac and Cdc42 GTPases regulate the organization of the actin cytoskeleton. Curr Opin Cell Biol 9:86-92, 1997
44. Du W, Liebowitz P, Prendergast G: Cell growth inhibition by farnesyltransferase inhibitors is mediated by gain of gernylgeranylated Rho B. Mol Cell Biol 19:1831-1840, 1999
45. Venet M, Angibaud P, Sanz G, et al: Synthesis and in-vitro structure-activity relationships of imidazolyl-2-quinolinones as farnesyl protein transferase inhibitors (FTI). Proc Am Assoc Cancer Res 39:318, 1998
46. Skrzat S, Angibaud P, Venet M, et al: R115777, a novel imidazole farnesyl protein transferase inhibitor (FTI) with potent oral antitumor activity. Proc Am Assoc Cancer Res 39:316, 1998 (abstr)
47. Miyake Y, Horiguchi M, Tomita N, et al: Occult macular dystrophy. Am J Ophthalmol 122:644-653, 1996
48. Pittler SJ, Fliesler SJ, Fisher PL, et al: In vivo requirement of protein prenylation for maintenance of retinal cytoarchitecture and photoreceptor structure. J Cell Biol 130:431-439, 1995
49. Christian MC, Korn EL: The limited precision of phase I trials. J Natl Cancer Inst 86:1662-1663, 1994 (editorial; comment)
50. Simon R, Freidlin B, Rubinstein L, et al: Accelerated titration designs for phase I clinical trials in oncology. J Natl Cancer Inst 89:1138-1147, 1997
51. Gibaldi M, Perier D: Pharmacokinetics. New York, NY, Marcel Dekker, Inc (1982)
52. Yan N, Ricca C, Fletcher J, et al: Farnesyltransferase inhibitors block the neurofibromatosis type I (NF1) malignant phenotype. Cancer Res 55:3569-3575, 1995
53. Nociari MM, Telford W, Russo C: Postthymic development of CD28-CD8+ T cell subset: Age-associated expansion and shift from memory to naive phenotype. J Immunol 162:3327-3335, 1999
54. d'Angeac AD, Monier S, Pilling D, et al: CD57+ T lymphocytes are derived from CD57-precursors by differentiation occurring in late immune responses. Eur J Immunol 24:1503-1511, 1994
55. Broers JL, Machiels BM, Kuijpers HJ, et al: A- and B-type lamins are differentially expressed in normal human tissues. Histochem Cell Biol 107:505-517, 1997
56. Moasser MM, Sepp-Lorenzino L, Kohl NE, et al: Farnesyl transferase inhibitors cause enhanced mitotic sensitivity to Taxol and epothilones. Proc Natl Acad Sci USA 95:1369-1374, 1998
57. Peli J, Schroter M, Rudaz C, et al: Oncogenic Ras inhibits Fas ligand-mediated apoptosis by downregulating the expression of Fas. Embo J 18:1824-1831, 1999
58. Gomez J, Gonzalez A, Martinez AC, et al: IL-2-induced cellular events. Crit Rev Immunol 18:185-220, 1998
59. Downward J: Ras signalling and apoptosis. Curr Opin Genet Dev 8:49-54, 1998
60. Mackall C, Hakim F, Gress R: T cell regeneration: All repertoires are not created equal. Immunol Today 18:245-251, 1997
61. Ho DD, Neumann AU, Perelson AS, et al: Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373:123-126, 1995 (see comments)
62. Hakim FT, Cepeda R, Kaimei S, et al: Constraints on CD4 recovery postchemotherapy in adults: Thymic insufficiency and apoptotic decline of expanded peripheral CD4 cells. Blood 90:3789-3798, 1997
63. Tanchot C, Rocha B: Peripheral selection of T cell repertoires: The role of continuous thymus output. J Exp Med 186:1099-1106, 1997
64. Gelmon KA, Eisenhaur EA, Harris AL, et al: Anticancer agents targeting signaling molecules and cancer cell environment: Challenges for drug development? J Natl Cancer Inst 91:1281-1287, 1999
65. Hudes G, Schol J, Baab J, et al: Phase I clinical and pharmacokinetic trial of the farnesyltransferase inhibitor R115777 on a 21-day dosing schedule. Proc Am Soc Clin Oncol 18:156a, 1999 (abstr)
66. Bernhard EJ, McKenna WG, Hamilton AD, et al: Inhibiting Ras prenylation increases the radiosensitivity of human tumor cell lines with activating mutations of ras oncogenes. Cancer Res 58:1754-1761, 1998
67. Prendergast GC, Davide JP, deSolms SJ, et al: Farnesyltransferase inhibition causes morphological reversion of ras-transformed cells by a complex mechanism that involves regulation of the actin cytoskeleton. Mol Cell Biol 14:4193-4202, 1994