Phase I trial and pharmacokinetic study of the farnesyltransferase inhibitor tipifarnib in children with refractory solid tumors or neurofibromatosis type I and plexiform neurofibromas

Journal of Clinical Oncology

Volumn 24, Issue 3, 2006, Pages 507-516

  Widemann, Brigitte C ^a   Salzer, Wanda L ^a   Arceci, Robert J ^a   Blaney, Susan M ^a   Fox, Elizabeth ^a   End, David ^a   Gillespie, Andrea ^a   Whitcomb, Patricia ^a   Palumbo, Joseph S ^a   Pitney, Aaron ^a   Jayaprakash, Nalini ^a   Zannikos, Peter ^a   Balis, Frank M ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHAPERONE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; PROTEIN HDJ 2; TIPIFARNIB; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; ENZYME INHIBITOR; FARNESYL TRANS TRANSFERASE; QUINOLONE DERIVATIVE;

ABDOMINAL DISCOMFORT; ABNORMAL RESPIRATORY SOUND; ACNE; ADOLESCENT; ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANEMIA; ANOREXIA; AREA UNDER THE CURVE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; ASTHENIA; BONE MARROW SUPPRESSION; CHILD; CHOLESTEROL BLOOD LEVEL; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DEHYDRATION; DIARRHEA; DIZZINESS; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DOSE INCREASE; DRUG FORMULATION; DRUG MECHANISM; DRUG TOLERABILITY; DRY SKIN; DYSPEPSIA; DYSPNEA; DYSURIA; ECZEMA; ENZYME ACTIVITY; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; FEVER; FLATULENCE; FLUSHING; GAIT DISORDER; GASTROESOPHAGEAL REFLUX; HEADACHE; HUMAN; HYPOKALEMIA; INSOMNIA; LEUKOPENIA; LYMPHADENOPATHY; LYMPHOCYTOPENIA; MALE; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; MUSCLE SPASM; MYALGIA; NAUSEA; NEUROFIBROMA; NEUROFIBROMATOSIS; NEUTROPENIA; OLIGURIA; PAIN; PERIPHERAL BLOOD MONONUCLEAR CELL; PHASE 1 CLINICAL TRIAL; PIGMENTATION; PRIORITY JOURNAL; PRURITUS; RASH; RHINITIS; RIGOR; SENSORY NEUROPATHY; SIDE EFFECT; SOLID TUMOR; SOMNOLENCE; STEADY STATE; THIRST; THROMBOCYTOPENIA; TRIACYLGLYCEROL BLOOD LEVEL; URINARY FREQUENCY; URINARY TRACT INFECTION; VOMITING; WEIGHT REDUCTION; BONE MARROW; DRUG ADMINISTRATION; DRUG ANTAGONISM; DRUG EFFECT; DRUG ERUPTION; GASTROINTESTINAL TRACT; PRESCHOOL CHILD; TREATMENT OUTCOME;

ADOLESCENT; ANTINEOPLASTIC AGENTS; BONE MARROW; CHILD; CHILD, PRESCHOOL; DRUG ADMINISTRATION SCHEDULE; DRUG ERUPTIONS; ENZYME INHIBITORS; FARNESYLTRANSTRANSFERASE; FEMALE; GASTROINTESTINAL TRACT; HUMANS; MALE; NEUROFIBROMA, PLEXIFORM; NEUROFIBROMATOSIS 1; QUINOLONES; TREATMENT OUTCOME;

EID: 33644838556     PISSN: 0732183X     EISSN: None     Source Type: Journal    
DOI: 10.1200/JCO.2005.03.8638     Document Type: Article

References (28)

1. Olson MF, Marais R: Ras protein signalling. Semin Immunol 12:63-73, 2000
2. Rodenhuis S: Ras and human tumors. Cancer Biol 3:241-247, 1992
3. Stirewalt DL, Meshinchi S, Radich JP: Molecular targets in acute myelogenous leukemia. Blood Rev 17:15-23, 2003
4. Cichowski K, Jacks T: NF1 tumor suppressor gene function: Narrowing the GAP. Cell 104:593-604, 2001
5. Korf B: Plexiform neurofibromas. Am J Med Genet 89:31-37, 1999
6. Evans DG, Baser ME, McGaughran J, et al: Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet 39:311-314, 2002
7. Adjei AA: Blocking oncogenic Ras signaling for cancer therapy. J Natl Cancer Inst 93:1062-1074, 2001
8. Weiss B, Bollag G, Shannon K: Hyperactive Ras as a therapeutic target in neurofibromatosis type 1. Am J Med Genet 89:14-22, 1999
9. Rowinsky E, Windle J, Von Hoff D: Ras protein farnesyltransferse: A strategic target for anticancer therapeutic development. J Clin Oncol 17:3631-3652, 1999
10. Lancet JE, Karp JE: Farnesyltransferase inhibitors in hematologic malignancies: New horizons in therapy. Blood 102:3880-3889, 2003
11. Santos ES, Rosenblatt JD, Goodman M: Role of farnesyltransferase inhibitors in hematologic malignancies. Expert Rev Anticancer Ther 4:843-856, 2004
12. 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
13. Zujewski J, Horak I, Boi R, et al: Phase I and pharmacokinetic study of farnesyl protein transferase inhibitor R115777 in advanced cancer. J Clin Oncol 18:927-941, 2000
14. Punt CJ, van Maanen L, Boi CJ, et al: 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
15. Lara PN Jr, Law LY, Wright JJ, et al: Intermittent dosing of the farnesyl transferase inhibitor tipifarnib (R115777) in advanced malignant solid tumors: A phase I California Cancer Consortium Trial. Anticancer Drugs 16:317-321, 2005
16. Crul M, de Klerk GJ, Swart M, et al: Phase I clinical and pharmacologic study of chronic oral administration of the farnesyl protein transferase inhibitor R115777 in advanced cancer. J Clin Oncol 20:2726-2735, 2002
17. Sparreboom A, Kehrer DF, Mathijssen RH, et al: Phase I and pharmacokinetic study of irinotecan in combination with R115777, a farnesyl protein transferase inhibitor. Br J Cancer 90:1508-1515, 2004
18. Patnaik A, Eckhardt SG, Izbicka E, et al: A phase I, pharmacokinetic, and biological study of the farnesyltransferase inhibitor tipifarnib in combination with gemcitabine in patients with advanced malignancies. Clin Cancer Res 9:4761-4771, 2003
19. Lebowitz PF, Eng-Wong J, Widemann BC, et al: 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
20. Adjei AA, Croghan GA, Erlichman C, et al: A phase I trial of the farnesyl protein transferase inhibitor R115777 in combination with gemcitabine and cisplatin in patients with advanced cancer. Clin Cancer Res 9:2520-2526, 2003
21. Cohen SJ, Ho L, Ranganathan S, et al: Phase II and pharmacodynamic study of the farnesyltransferase inhibitor R115777 as initial therapy in patients with metastatic pancreatic adenocarcinoma. J Clin Oncol 21:1301-1306, 2003
22. Johnston SR, Ellis PA, Houston S, et al: A phase II study of the farnesyltransferase inhibitor R115777 in patients with advanced breast cancer. Proc Am Soc Clin Oncol 18:83a, 2000 (suppl; abstr 318)
23. 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
24. 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
25. End D: Farnesyl protein transferase inhibitors and other therapies targeting the Ras signal transduction pathway. Invest New Drugs 17:241-258, 1999
26. Miller AB, Hoogstraten B, Staquet M, et al: Reporting results of cancer treatment. Cancer 47: 207-214, 1981
27. Zimmerman TM, Harlin H, Odenike OM, et al: Dose-ranging pharmacodynamic study of tipifarnib (R115777) in patients with relapsed and refractory hematologic malignancies. J Clin Oncol 22:4816-4822, 2004
28. 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