Degree(s):
BS, Santa Clara University, 1987
PhD, University of Nevada, 1992
Postdoc, Colorado State University & University of Colorado-HSC,
1993-1996
Research Interests:
My laboratory focuses on drugs used in the treatment of cancer.
This includes drug pharmacokinetics and pharmacodynamics and how
to optimize drug use in the clinic. An important component of cancer
drug therapy is drug combinations, and a focus of our studies is
what drugs to combine and in what manner with regards to dose and
scheduling.
Current projects in the laboratory include:
- Combinations of tyrosine kinase inhibitors and cytotoxic chemotherapy
in tumor xenograft models.
- Treatment of melanoma with MAP-kinase pathway inhibitors and drug
combinations.
- Development of mouse models of cancer that follow a more normal
progression of natural disease including post-surgical models.
- Physiologically-based modeling of drug pharmacokinetics coupled
to Monte Carlo simulation to predict variability in drug exposure
in special populations.
- Interspecies scaling of drug dosing for equivalent drug effects.
Selected Publications:
Gustafson, D.L., Bradshaw-Pierce, E.L., Merz, A.L., and Zirrolli,
J.A. (2006). Tissue distribution and metabolism of ZD6474 in tumor
bearing nude mice following oral dosing. J Pharmacol Exp Therap
318:872-880.
Basche, M., Gustafson, D.L., Holden, S.N., O'Bryant, C.L., Gore,
L., Witta, S., Schultz, M.K., Morrow, M., Grolnic, S., Conrad, D.,
Levin, A., Creese, B.R., Kangas, M., Roberts, K., Nguyen, T., Davis,
K., Addison, R.S., Moore, J. and Eckhardt, S.G. (2006). A phase
I and pharmacokinetic study of PI-88 in patients with advanced solid
tumors. Clin Cancer Res 12:5471-5480.
Guo, W., Reigan, P., Siegel, D., Zirrolli, J., Gustafson, D. and
Ross, D. (2006). The bioreduction of a series of benzoquinone ansamycins
by NAD(P)H:quinone oxidoreductase 1 (NQO1) to more potent heat shock
protein 90 (HSP90) inhibitors, the hydroquinone ansamycins. Mol
Pharmacol 70:1194-1203.
Flaig, T.W., Gustafson, D.L., Su, L-J., Zirrolli, J., Harrison,
G., Pierson, A.S., Agarwal, R. and Glode, L.M. (2007). A phase I
and pharmacokinetic study of silybinin phytosome in prostate cancer
patients. Invest New Drugs 25:139-146.
Gustafson. D.L., Frederick, B., Merz, A.L. and Raben, D. (2007).
Dose scheduling of the dual VEGFR and EGFR tyrosine kinase inhibitor
vandetanib (ZD6474, Zactima®) in combination with radiotherapy
in EGFR-positive and EGFR-null human head and neck tumor xenografts.
Cancer Chemother Pharmacol EPub, 3/29/2007.
Lana, S., U’ren, L., Plaza, S., Elmslie, R., Gustafson, D.
and Dow, S. (2007). Comparison of continuous low-dose oral chemotherapy
with conventional doxorubicin chemotherapy for adjuvant therapy
of hemangiosarcoma in dogs. J Vet Intern Med 21:764-769.
Bradshaw-Pierce, E.L., Eckhardt, S.G. and Gustafson, D.L. (2007).
A physiologically-based pharmacokinetic model of docetaxel disposition:
from mouse to man. Clin Cancer Res 13:2768-2776.
Troiani, T., Serkova, N.J., Gustafson, D.L., Henthorn, T.K., Lockerbie,
O., Morrow, M., Ciardiello, F., and Eckhardt, S.G. (2007). Antitumor
efficacy of vandetanib (ZD6474), a dual VEGFR/EGFR inhibitor, in
combination with irinotecan in a human colorectal cancer xenograft
model. Clin Cancer Res (In Press).
