As a member of the Pharmacology and Experimental Therapeutics (PET) Section I am involved in the development of new agents for childhood cancers, particularly the application of new molecularly targeted drugs. The primary objective of this project is to develop new agents for the treatment of childhood cancers with an emphasis on a more rational, targeted approach of drug development based on the current understanding of the molecular pathogenesis of human cancers. New molecularly targeted agents that are undergoing clinical development for adult cancers will be applied to childhood cancers based on the mechanism of action of the drug and the importance of the target in childhood cancers. The development of the raf kinase and receptor tyrosine kinase inhibitor sorafenib for children with refractory cancers serves as an example. In addition, the clinical development of novel cytotoxic agents for childhood cancers, such as the epothilone B analog ixabepilone (BMS-247550), an antitubulin agent, which inhibits tubulin depolymerization, will also be pursued. The pharmacokinetics and pharmacodynamics of these drugs will be studied and compared to results in adults. The development of the methotrexate (MTX) rescue agent carboxypeptidase-G2 (CPDG2) will be continued until FDA approval for this potentially life-saving treatment has been achieved.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01SC010354-08
Application #
7594814
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2007
Total Cost
$330,554
Indirect Cost
Name
National Cancer Institute Division of Clinical Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Widemann, Brigitte C; Goodspeed, Wendy; Goodwin, Anne et al. (2009) Phase I trial and pharmacokinetic study of ixabepilone administered daily for 5 days in children and adolescents with refractory solid tumors. J Clin Oncol 27:550-6
Kim, AeRang; Balis, Frank M; Widemann, Brigitte C (2009) Sorafenib and sunitinib. Oncologist 14:800-5
Balis, F M; Fox, E; Widemann, B C et al. (2009) Clinical drug development for childhood cancers. Clin Pharmacol Ther 85:127-9
Widemann, Brigitte C; Salzer, Wanda L; Arceci, Robert J et al. (2006) Phase I trial and pharmacokinetic study of the farnesyltransferase inhibitor tipifarnib in children with refractory solid tumors or neurofibromatosis type I and plexiform neurofibromas. J Clin Oncol 24:507-16
Fox, Elizabeth; Maris, John M; Widemann, Brigitte C et al. (2006) A phase 1 study of ABT-751, an orally bioavailable tubulin inhibitor, administered daily for 7 days every 21 days in pediatric patients with solid tumors. Clin Cancer Res 12:4882-7
Widemann, Brigitte C; Adamson, Peter C (2006) Understanding and managing methotrexate nephrotoxicity. Oncologist 11:694-703
Stephens, Michael C; Baldassano, Robert N; York, Amy et al. (2005) The bioavailability of oral methotrexate in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 40:445-9
Lebowitz, Peter F; Eng-Wong, Jennifer; Widemann, Brigitte C et al. (2005) A phase I trial and pharmacokinetic study of tipifarnib, a farnesyltransferase inhibitor, and tamoxifen in metastatic breast cancer. Clin Cancer Res 11:1247-52
Adamson, P C; Blaney, S M; Widemann, B C et al. (2004) Pediatric phase I trial and pharmacokinetic study of the platelet-derived growth factor (PDGF) receptor pathway inhibitor SU101. Cancer Chemother Pharmacol 53:482-8
Widemann, Brigitte C (2004) Merlin PAKs a punch. Cancer J 10:8-11

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