Phase I and Pharmacokinetic Study of the Oral Farnesyltransferase Inhibitor Lonafarnib Administered Twice Daily to Pediatric Patients With Advanced Central Nervous System Tumors Using a Modified Continuous Reassessment Method: A Pediatric Brain Tumor Consortium Study
作者： Mark W. Kieran , Roger J. Packer , Arzu Onar , Susan M. Blaney , Peter Phillips
关键词: Pediatric Brain Tumor Consortium 、 Dose 、 Lonafarnib 、 Survival analysis 、 Medicine 、 Pneumonitis 、 Pharmacokinetics 、 Oncology 、 Central nervous system disease 、 Farnesyltransferase inhibitor 、 Internal medicine 、 Surgery
摘要: Purpose A dose-escalation phase I and pharmacokinetic study of the farnesyltransferase inhibitor lonafarnib (SCH66336) was conducted in children with recurrent or progressive CNS tumors. Primary objectives were to estimate maximum-tolerated dose (MTD) describe dose-limiting toxicities (DLTs) pharmacokinetics lonafarnib. Farnesylation inhibition HDJ-2 peripheral blood also measured. Patients Methods Lonafarnib administered orally twice daily at levels 70, 90, 115, 150, 200 mg/m2/dose bid. modified continual reassessment method (CRM) used MTD based on actual dosages observed during initial 4 weeks treatment. Results Fifty-three brain tumors enrolled, a median age 12.2 years (range, 3.9 19.5 years). Dose-limiting pneumonitis myelosuppression three patients level. relatively constant...
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jco.org参考文章(35)
Masanori Kurimoto, Yutaka Hirashima, Hideo Hamada, Hironaga Kamiyama, Shoichi Nagai, Nakamasa Hayashi, Shunro Endo, In vitro and in vivo growth inhibition of human malignant astrocytoma cells by the farnesyltransferase inhibitor B1620 Journal of Neuro-oncology. ,vol. 61, pp. 103- 112 ,(2003) , 10.1023/A:1022132201313
Dirk Vordermark, Jörg Christian Tonn, Klaus Roosen, Hakim L. Bouterfa, Vera Sattelmeyer, Stefanie Czub, Inhibition of Ras farnesylation by lovastatin leads to downregulation of proliferation and migration in primary cultured human glioblastoma cells. Anticancer Research. ,vol. 20, pp. 2761- 2771 ,(2000)
Phyllis A. Svingen, Alex A. Adjei, Scott H. Kaufmann, Jeff A. Sloan, Randolph S. Marks, Jenny N. Davis, Paul Kirschmeier, Lorelei J. Hanson, Charles Erlichman, W. Robert Bishop, Pamela Atherton, David L. Cutler, A Phase I Trial of the Farnesyl Transferase Inhibitor SCH66336: Evidence for Biological and Clinical Activity Cancer Research. ,vol. 60, pp. 1871- 1877 ,(2000)
Walter A. Korfmacher, Amin A. Nomeir, Jianping Chen, Loretta Nielsen, Lynn Wang, Joseph J. Catino, Matthew S. Bryant, Janet Dell, Suining Lee, Viyyoor M. Girijavallabhan, Paul Kirschmeier, Jameel Syed, Michael Malkowski, Eric Ferrari, W. Robert Bishop, Bohdan Yaremko, Ronald J. Doll, Alan K. Mallams, Arthur G. Taveras, Ming Liu, Dineshwar Sinha, C-C. Lin, Phil Lipari, Stacy Remiszewski, F. George Njoroge, Nicholas Prioli, 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 Research. ,vol. 58, pp. 4947- 4956 ,(1998)
Ferry A.L.M. Eskens, Ahmad Awada, David L. Cutler, Maja J.A. de Jonge, Gré P.M. Luyten, Marije N. Faber, Paul Statkevich, Alex Sparreboom, Jaap Verweij, Axel-R. Hanauske, Martine Piccart, Phase I and Pharmacokinetic Study of the Oral Farnesyl Transferase Inhibitor SCH 66336 Given Twice Daily to Patients With Advanced Solid Tumors Journal of Clinical Oncology. ,vol. 19, pp. 1167- 1175 ,(2001) , 10.1200/JCO.2001.19.4.1167
S Mishra, B Zhang, J Groffen, N Heisterkamp, A farnesyltransferase inhibitor increases survival of mice with very advanced stage acute lymphoblastic leukemia/lymphoma caused by P190 Bcr/Abl. Leukemia. ,vol. 18, pp. 23- 28 ,(2004) , 10.1038/SJ.LEU.2403203
Ahmad Awada, Ferry ALM Eskens, M Piccart, DL Cutler, Ate van der Gaast, Harry Bleiberg, Jantien Wanders, MN Faber, Paul Statkevich, Pierre Fumoleau, Jaap Verweij, EORTC Early Clinical Studies Group, Phase I and pharmacological study of the oral farnesyltransferase inhibitor SCH 66336 given once daily to patients with advanced solid tumours European Journal of Cancer. ,vol. 38, pp. 2272- 2278 ,(2002) , 10.1016/S0959-8049(02)00379-9
Ji-Youn Han, Seung Hyun Oh, Floriana Morgillo, Jeffrey N Myers, Edward Kim, Waun Ki Hong, Ho-Young Lee, None, Hypoxia-inducible Factor 1α and Antiangiogenic Activity of Farnesyltransferase Inhibitor SCH66336 in Human Aerodigestive Tract Cancer Journal of the National Cancer Institute. ,vol. 97, pp. 1272- 1286 ,(2005) , 10.1093/JNCI/DJI251
Ian F. Pollack, Markus Bredel, Melanie Erff, Andrew D. Hamilton, Said M. Sebti, Inhibition of Ras and related guanosine triphosphate-dependent proteins as a therapeutic strategy for blocking malignant glioma growth: II--preclinical studies in a nude mouse model. Neurosurgery. ,vol. 45, pp. 1208- 1215 ,(1999) , 10.1097/00006123-199911000-00039
Jonathan E. Rosenberg, Hans von der Maase, John D. Seigne, Jozef Mardiak, David J. Vaughn, Malcolm Moore, Deepak Sahasrabudhe, Peter A. Palmer, Juan Jose Perez-Ruixo, Eric J. Small, A phase II trial of R115777, an oral farnesyl transferase inhibitor, in patients with advanced urothelial tract transitional cell carcinoma. Cancer. ,vol. 103, pp. 2035- 2041 ,(2005) , 10.1002/CNCR.21023