DF/HCC Program Affiliation

Member, Translational Pharmacology and Early Therapeutic Trials Program
Member, Gastrointestinal Malignancies Program

DF/HCC Associations

Member, Center Scientific Council
Director, Cancer Pharmacology Core

Research Abstract

The principal focus of my research involves bioanalytical method development and elucidating the pharmacokinetic behavior and metabolism of investigational chemotherapeutic agents during phase I/II clinical trials in cancer patients. The activity of an anticancer drug ultimately depends on the ability of the agent itself, or an active metabolite derived from it, to migrate from the administration site through the body to the tumor. Similarly, toxicities result from the exposure of normal tissues to the drug. These pharmacological effects can generally be related to the time course of the concentration of drug in blood or plasma. Accordingly, serial measurements of the plasma concentration of a drug following its administration has become an integral component of phase I clinical studies of investigational anticancer agents. This information provides the basis for establishing the pharmacokinetic behavior of a drug, the objective of which is to mathematically describe the processes involving drug absorption, distribution, and elimination from the body. The acquisition of pharmacokinetic data during the phase I evaluation of an anticancer agent in is a critical element in developing a rational scheme for the route, dose and frequency of drug administration for optimal therapeutic benefit.

Publications

• Grossman SA, Carson KA, Batchelor TT, Lesser G, Mikkelsen T, Alavi JB, Phuphanich S, Hammour T, Fisher JD, Supko JG. The effect of enzyme-inducing antiseizure drugs on the pharmacokinetics and tolerability of procarbazine hydrochloride. Clin Cancer Res 2006 Sep 1; 12(17):5174-81
  PMID: 16951236
• Garcia-Carbonero R, Supko JG, Maki RG, Manola J, Ryan DP, Harmon D, Puchalski TA, Goss G, Seiden MV, Waxman A, Quigley MT, Lopez T, Sancho MA, Jimeno J, Guzman C, Demetri GD. Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter phase II and pharmacokinetic study. J Clin Oncol 2005 Aug 20; 23(24):5484-92
  PMID: 16110008
• Goffin JR, Anderson IC, Supko JG, Eder JP, Shapiro GI, Lynch TJ, Shipp M, Johnson BE, Skarin AT. Phase I trial of the matrix metalloproteinase inhibitor marimastat combined with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer. Clin Cancer Res 2005 May 1; 11(9):3417-24
  PMID: 15867243
• Lau L, Supko JG, Blaney S, Hershon L, Seibel N, Krailo M, Qu W, Malkin D, Jimeno J, Bernstein M, Baruchel S. A phase I and pharmacokinetic study of ecteinascidin-743 (Yondelis) in children with refractory solid tumors. A Children's Oncology Group study. Clin Cancer Res 2005 Jan 15; 11(2 Pt 1):672-7
  PMID: 15701855
• Ryan DP, Eder JP, Puchlaski T, Seiden MV, Lynch TJ, Fuchs CS, Amrein PC, Sonnichsen D, Supko JG, Clark JW. Phase I clinical trial of the farnesyltransferase inhibitor BMS-214662 given as a 1-hour intravenous infusion in patients with advanced solid tumors. Clin Cancer Res 2004 Apr 1; 10(7):2222-30
  PMID: 15073096
• Zhu AX, Puchalski TA, Stanton VP, Ryan DP, Clark JW, Nesbitt S, Charlat O, Kelly P, Kreconus E, Chabner BA, Supko JG. Dihydropyrimidine dehydrogenase and thymidylate synthase polymorphisms and their association with 5-fluorouracil/leucovorin chemotherapy in colorectal cancer. Clin Colorectal Cancer 2004 Feb; 3(4):225-34
  PMID: 15025795
• He X, Batchelor TT, Grossman S, Supko JG. Determination of procarbazine in human plasma by liquid chromatography with electrospray ionization mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2004 Jan 25; 799(2):281-91
  PMID: 14670747
• Supko JG, Eder JP, Ryan DP, Seiden MV, Lynch TJ, Amrein PC, Kufe DW, Clark JW. Phase I clinical trial and pharmacokinetic study of the spicamycin analog KRN5500 administered as a 1-hour intravenous infusion for five consecutive days to patients with refractory solid tumors. Clin Cancer Res 2003 Nov 1; 9(14):5178-86
  PMID: 14613997
• Puchalski TA, Ryan DP, Garcia-Carbonero R, Demetri GD, Butkiewicz L, Harmon D, Seiden MV, Maki RG, Lopez-Lazaro L, Jimeno J, Guzman C, Supko JG. Pharmacokinetics of ecteinascidin 743 administered as a 24-h continuous intravenous infusion to adult patients with soft tissue sarcomas: associations with clinical characteristics, pathophysiological variables and toxicity. Cancer Chemother Pharmacol 2002 Oct; 50(4):309-19
  PMID: 12357306