A phase 2 study of the farnesyltransferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myelogenous leukemia

Blood

Volumn 109, Issue 4, 2007, Pages 1387-1394

  Lancet, Jeffrey E ^a   Gojo, Ivana ^b   Gotlib, Jason ^c   Feldman, Eric J ^d   Greer, Jacqueline ^j   Liesveld, Jane L ^e   Bruzek, Laura M ^f   Morris, Lawrence ^g   Park, Youn ^h   Adjei, Alex A ^f   Kaufmann, Scott H ^f   Garrett Mayer, Elizabeth ^j   Greenberg, Peter L ^c   Wright, John J ⁱ   Karp, Judith E ^j  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF MARYLAND   (United States)

^c STANFORD CANCER INSTITUTE   (United States)

^d WEILL CORNELL MEDICAL COLLEGE   (United States)

^e UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^f MAYO CLINIC   (United States)

^g Blood and Marrow Transplant Group of Georgia   (United States)

^h JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

ⁱ NATIONAL CANCER INSTITUTE   (United States)

^j JOHNS HOPKINS UNIVERSITY   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN FARNESYLTRANSFERASE INHIBITOR; TIPIFARNIB;

ACUTE GRANULOCYTIC LEUKEMIA; ADULT; AGED; ARTICLE; ATAXIA; BONE MARROW CULTURE; CANCER PATIENT; CANCER RISK; CANCER SURGERY; CLINICAL TRIAL; CONFUSION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DRUG ERUPTION; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; GERIATRIC PATIENT; HUMAN; INFECTION; KIDNEY FAILURE; LEUKEMIA REMISSION; LIVER TOXICITY; MAJOR CLINICAL STUDY; MALE; METABOLIC DISORDER; MULTICENTER STUDY; MYELODYSPLASTIC SYNDROME; NAUSEA; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PHASE 2 CLINICAL TRIAL; POOR GENERAL CONDITION; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SIDE EFFECT; SURVIVAL RATE; SURVIVAL TIME; THERAPY EFFECT; TREATMENT OUTCOME; TREATMENT RESPONSE; UROGENITAL TRACT DISEASE; VOMITING;

EID: 33847001315     PISSN: 00064971     EISSN: 00064971     Source Type: Journal    
DOI: 10.1182/blood-2006-04-014357     Document Type: Article

References (44)

1. Godwin JE, Kopecky KJ, Head DR, et al. A double-blind placebo-controlled trial of granulocyte colony-stimulating factor in elderly patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group Study (9031). Blood. 1998;91:3607-3615.
2. Goldstone AH, Burnett AK, Wheatley K, et al. Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial. Blood. 2001;98:1302-1311.
3. Leith CP, Kopecky KJ, Godwin J, et al. Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study. Blood. 1997;89:3323-3329.
4. Leith CP, Kopecky KJ, Chen IM, et al. Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: a Southwest Oncology Group Study. Blood. 1999;94:1086-1099.
5. Lowenberg B, Zittoun R, Kerkhofs H, et al. On the value of intensive remission-induction chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: a randomized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group. J Clin Oncol. 1989;7:1268-1274.
6. Lowenberg B, Suciu S, Archimbaud E, et al. Use of recombinant GM-CSF during and after remission induction chemotherapy in patients aged 61 years and older with acute myeloid leukemia: final report of AML-11, a phase III randomized study of the Leukemia Cooperative Group of European Organisation for the Research and Treatment of Cancer and the Dutch Belgian Hemato-Oncology Cooperative Group. Blood. 1997;90:2952-2961.
7. Rowe JM, Andersen JW, Mazza JJ, et al. A randomized placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (> 55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490). Blood. 1995;86:457-462.
8. Archimbaud E, Jehn U, Thomas X, et al. Multicenter randomized phase II trial of idarubicin vs mitoxantrone, combined with VP-16 and cytarabine for induction/consolidation therapy, followed by a feasibility study of autologous peripheral blood stem cell transplantation in elderly patients with acute myeloid leukemia. Leukemia. 1999;13:843-849.
9. Cassileth PA, Harrington DP, Appelbaum FR, et al. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med. 1998;339:1649-1656.
10. Stone RM, Berg DT, George SL, et al. Postremission therapy in older patients with de novo acute myeloid leukemia: a randomized trial comparing mitoxantrone and intermediate-dose cytarabine with standard-dose cytarabine. Blood. 2001;98:548-553.
11. End DW. Farnesyl protein transferase inhibitors and other therapies targeting the Ras signal transduction pathway. Invest New Drugs. 1999;17:241-258.
12. Rowinsky EK, Windle JJ, Von Hoff DD. Ras protein farnesyltransferase: a strategic target for anticancer therapeutic development. J Clin Oncol. 1999;17:3631-3652.
13. 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.
14. Ashar HR, James L, Gray K, et al. The farnesyl transferase inhibitor SCH 66336 induces a G(2)→M or G(1) pause in sensitive human tumor cell lines. Exp Cell Res. 2001;262:17-27.
15. Feldkamp MM, Lau N, Guha A. Growth inhibition of astrocytoma cells by farnesyl transferase inhibitors is mediated by a combination of anti-proliferative, pro-apoptotic and anti-angiogenic effects. Oncogene. 1999;18:7514-7526.
16. Lebowitz PF, Sakamuro D, Prendergast GC. Farnesyl transferase inhibitors induce apoptosis of Ras-transformed cells denied substratum attachment. Cancer Res. 1997;57:708-713.
17. Lebowitz PF, Prendergast GC. Non-Ras targets of farnesyltransferase inhibitors: focus on Rho. Oncogene. 1998;17:1439-1445.
18. Liu A, Du W, Liu JP, Jessell TM, Prendergast GC. RhoB alteration is necessary for apoptotic and antineoplastic responses to farnesyltransferase inhibitors. Mol Cell Biol. 2000;20:6105-6113.
19. 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. 1995;55:5302-5309.
20. Zhang B, Prendergast GC, Fenton RG. Farnesyltransferase inhibitors reverse Ras-mediated inhibition of Fas gene expression. Cancer Res. 2002;62:450-458.
21. 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.
22. Gotlib J, Loh M, Lancet JE, et al. Phase I/II study of farnesyltransferase inhibitor R115777 (Zarnestra) in patients with myeloproliferative disorders (MPDs): interim results [abstract]. Blood. 2003;102:3425a.
23. 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 I clinical-correlative trial. Blood. 2001;97:3361-3369.
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.
25. 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.
26. List AF, DeAngelo D, O'Brien S, et al. Phase I study of continuous oral administration of lonafarnib (Sarasar™) in patients with advanced hematologic malignancies [abstract]. Blood. 2002;100:789a.
27. 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. 2001;61:131-137.
28. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100:2292-2302.
29. Slovak ML, Kopecky KJ, Cassileth PA, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study. Blood. 2000;96:4075-4083.
30. Byrd JC, Mrozek K, Dodge RK, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood. 2002;100:4325-4336.
31. Wolman SR, Gundacker H, Appelbaum FR, Slovak ML. Impact of trisomy 8 (+8) on clinical presentation, treatment response, and survival in acute myeloid leukemia: a Southwest Oncology Group study. Blood. 2002;100:29-35.
32. Adjei AA, Davis JN, Erlichman C, Svingen PA, Kaufmann SH. Comparison of potential markers of farnesyltransferase inhibition. Clin Cancer Res. 2000;6:2318-2325.
33. Sinensky M, Fantle K, Dalton M. An antibody which specifically recognizes prelamin A but not mature lamin A: application to detection of blocks in farnesylation-dependent protein processing. Cancer Res. 1994;54:3229-3232.
34. Kaufmann SH. Expression of nuclear envelope lamins A and C in human myeloid leukemias. Cancer Res. 1992;52:2847-2853.
35. Adjei AA, Erlichman C, Davis JN, et al. A phase I trial of the farnesyl transferase inhibitor SCH66336: evidence for biological and clinical activity. Cancer Res. 2000;60:1871-1877.
36. Dalton MB, Fantle KS, Bechtold HA, et al. The farnesyl protein transferase inhibitor BZA-5B blocks farnesylation of nuclear lamins and p21ras but does not affect their function or localization. Cancer Res. 1995;55:3295-3304.
37. Lancet JE, Willman CL, Bennett JM. Acute myelogenous leukemia and aging: clinical interactions. Hematol Oncol Clin North Am. 2000;14:251-267.
38. Litzow MR. The therapy of relapsed acute leukaemia in adults. Blood Rev. 2004;18:39-63.
39. Appelbaum FR, Gundacker H, Head DR, et al. Age and acute myeloid leukemia. Blood. 2006;107:3481-3485.
40. Kantarjian H, O Brien S, Cortes J, et al. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome. Cancer. 2006;106:1090-1098.
41. Baer MR, George SL, Dodge RK, et al. Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720. Blood 2002;100:1224-1232.
42. Lowenberg B, Suciu S, Archimbaud E, et al. Mitoxantrone versus daunorubicin in induction-consolidation chemotherapy - the value of low-dose cytarabine for maintenance of remission, and an assessment of prognostic factors in acute myeloid leukemia in the elderly: final report. European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology Cooperative Hovon Group. J Clin Oncol. 1998;16:872-881.
43. Stone RM, Berg DT, George SL, et al. Granulocyte-macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia. N Engl J Med. 1995;332:1671-1677.
44. Estey E, Thall P, Beran M, et al. Effect of diagnosis (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute myeloid leukemia [AML]) on outcome of AML-type chemotherapy. Blood. 1997;90:2969-2977.