Journal of the National Cancer Institute
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J. Natl. Cancer Inst. · Dec 2002
Role of body surface area in dosing of investigational anticancer agents in adults, 1991-2001.
The prescribed dose of anticancer agents is most commonly calculated using body surface area as the only independent variable, and it has been shown that this approach still results in large interpatient variability in drug exposure. Here, we retrospectively assessed the pharmacokinetics of 33 investigational agents tested in phase I trials from 1991 through 2001, as a function of body surface area in 1650 adult cancer patients. ⋯ These results do not support the use of body surface area in dose calculations and suggest that alternate dosing strategies should be evaluated. We conclude that body surface area should not be used to determine starting doses of investigational agents in future phase I studies.
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J. Natl. Cancer Inst. · Nov 2002
Potential use of imatinib in Ewing's Sarcoma: evidence for in vitro and in vivo activity.
Ewing's sarcoma cells express c-kit, a receptor tyrosine kinase, and its ligand, stem cell factor (SCF), creating a potential autocrine loop that may promote tumor survival. We thus examined whether the specific tyrosine kinase inhibitor imatinib mesylate (hereafter imatinib; formerly STI571) could inhibit the proliferation of Ewing's sarcoma cells in vitro and in vivo. ⋯ Imatinib interferes with growth of all Ewing's sarcoma cell lines tested in vitro and in vivo. Targeted inhibition of tyrosine kinase-dependent autocrine loops, therefore, may be a viable therapeutic strategy for Ewing's sarcoma.