DF/HCC Program Affiliation

Gastrointestinal Malignancies
Translational Pharmacology and Early Therapeutic Trials

DF/HCC Associations

Director, Cancer Pharmacology
Member, Center Scientific Council

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
  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 tis
  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 cance
  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.Cli
  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.
  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 i
  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.
  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 refrac
  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
  12357306
• Attar EC, De Angelo DJ, Supko JG, D'Amato F, Zahrieh D, Sirulnik A, Wadleigh M, Ballen KK, McAfee S, Miller KB, Levine J, Galinsky I, Trehu EG, Schenkein D, Neuberg D, Stone RM, Amrein PC.Phase I and pharmacokinetic study of bortezomib in combination with
  18316568
• Grossman SA, Olson J, Batchelor T, Peereboom D, Lesser G, Desideri S, Ye X, Hammour T, Supko JG.Effect of phenytoin on celecoxib pharmacokinetics in patients with glioblastoma.Neuro-oncol 2008 Apr;10(2):190-8.
  18287342
• McDermott U, Sharma SV, Dowell L, Greninger P, Montagut C, Lamb J, Archibald H, Raudales R, Tam A, Lee D, Rothenberg SM, Supko JG, Sordella R, Ulkus LE, Iafrate AJ, Maheswaran S, Njauw CN, Tsao H, Drew L, Hanke JH, Ma XJ, Erlander MG, Gray NS, Haber DA, S
  18077425
• Berkenblit A, Eder JP, Ryan DP, Seiden MV, Tatsuta N, Sherman ML, Dahl TA, Dezube BJ, Supko JG.Phase I clinical trial of STA-4783 in combination with paclitaxel in patients with refractory solid tumors.Clin Cancer Res 2007 Jan 15;13(2 Pt 1):584-90.
  17255281
• Meyerhardt JA, Clark JW, Supko JG, Eder JP, Ogino S, Stewart CF, D'Amato F, Dancey J, Enzinger PC, Zhu AX, Ryan DP, Earle CC, Mayer RJ, Michelini A, Kinsella K, Fuchs CS.Phase I study of gefitinib, irinotecan, 5-fluorouracil and leucovorin in patients wit
  17216531
• Ryan DP, O'Neil BH, Supko JG, Rocha Lima CM, Dees EC, Appleman LJ, Clark J, Fidias P, Orlowski RZ, Kashala O, Eder JP, Cusack JC.A Phase I study of bortezomib plus irinotecan in patients with advanced solid tumors.Cancer 2006 Dec 1;107(11):2688-97.
  17075878
• Ryan DP, Appleman LJ, Lynch T, Supko JG, Fidias P, Clark JW, Fishman M, Zhu AX, Enzinger PC, Kashala O, Cusack J, Eder JP.Phase I clinical trial of bortezomib in combination with gemcitabine in patients with advanced solid tumors.Cancer 2006 Nov 15;107(10
  17036355
• Krasner CN, Roche M, Horowitz NS, Supko JG, Lee SI, Oliva E.Case records of the Massachusetts General Hospital. Case 11-2006. A 54-year-old woman with a mass in the pelvis.N Engl J Med 2006 Apr 13;354(15):1615-25.
  16611953
• Eder JP, Ryan DP, Appleman L, Zhu AX, Puchalski T, He X, Sonnichsen DS, Cooper M, Wright J, Clark JW, Supko JG.Phase I clinical trial of the farnesyltransferase inhibitor BMS-214662 administered as a weekly 24 h continuous intravenous infusion in patients
  16362299
• Klein A, He X, Roche M, Mallett A, Duska L, Supko JG, Seiden MV.Prolonged stabilization of platinum-resistant ovarian cancer in a single patient consuming a fermented soy therapy.Gynecol Oncol 2005 Sep 16.
  16171852
• Amrein PC, Clark JR, Supko JG, Fabian RL, Wang CC, Colevas AD, Posner MR, Deschler DG, Rocco JW, Finkelstein DM, McIntyre JF.Phase I trial and pharmacokinetics of escalating doses of paclitaxel and concurrent hyperfractionated radiotherapy with or without
  16116597
• Grossman SA, Alavi JB, Supko JG, Carson KA, Priet R, Dorr FA, Grundy JS, Holmlund JT.Efficacy and toxicity of the antisense oligonucleotide aprinocarsen directed against protein kinase C-alpha delivered as a 21-day continuous intravenous infusion in patie
  15701280
• Merchan JR, Jayaram DR, Supko JG, He X, Bubley GJ, Sukhatme VP.Increased endothelial uptake of paclitaxel as a potential mechanism for its antiangiogenic effects: potentiation by Cox-2 inhibition.Int J Cancer 2005 Jan 20;113(3):490-8.
  15455390
• Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA.Activating mutations in the epidermal growth factor receptor underlying responsiveness
  15118073
• Garcia-Carbonero R, Supko JG, Manola J, Seiden MV, Harmon D, Ryan DP, Quigley MT, Merriam P, Canniff J, Goss G, Matulonis U, Maki RG, Lopez T, Puchalski TA, Sancho MA, Gomez J, Guzman C, Jimeno J, Demetri GD.Phase II and pharmacokinetic study of ecteinasc
  15084621
• Batchelor TT, Gilbert MR, Supko JG, Carson KA, Nabors LB, Grossman SA, Lesser GJ, Mikkelsen T, Phuphanich S,.Phase 2 study of weekly irinotecan in adults with recurrent malignant glioma: final report of NABTT 97-11.Neuro-oncol 2004 Jan;6(1):21-7.
  14769136
• Eder JP, Garcia-Carbonero R, Clark JW, Supko JG, Puchalski TA, Ryan DP, Deluca P, Wozniak A, Campbell A, Rothermel J, LoRusso P.A phase I trial of daily oral 4'- N -benzoyl-staurosporine in combination with protracted continuous infusion 5-Fluorouracil in
  14739662
• Campos SM, Matulonis UA, Penson RT, Lee H, Berkowitz RS, Duska LR, Fuller AF, Wilson KS, Puchalski TA, Supko JG, Seiden MV.Phase II study of liposomal doxorubicin and weekly paclitaxel for recurrent Müllerian tumors.Gynecol Oncol 2003 Sep;90(3):610-8.
  13678734
• Gilbert MR, Supko JG, Batchelor T, Lesser G, Fisher JD, Piantadosi S, Grossman S.Phase I clinical and pharmacokinetic study of irinotecan in adults with recurrent malignant glioma.Clin Cancer Res 2003 Aug 1;9(8):2940-9.
  12912940
• Laverdiere C, Kolb EA, Supko JG, Gorlick R, Meyers PA, Maki RG, Wexler L, Demetri GD, Healey JH, Huvos AG, Goorin AM, Bagatell R, Ruiz-Casado A, Guzman C, Jimeno J, Harmon D.Phase II study of ecteinascidin 743 in heavily pretreated patients with recurrent
  12910529
• Ryan DP, Puchalski T, Supko JG, Harmon D, Maki R, Garcia-Carbonero R, Kuhlman C, Winkelman J, Merriam P, Quigley T, Jimeno J, Manola J, Demetri GD.A phase II and pharmacokinetic study of ecteinascidin 743 in patients with gastrointestinal stromal tumors.O
  12490740
• Michaelson MD, Ryan DP, Fuchs CS, Supko JG, Garcia-Carbonero R, Paul Eder J, Clark JW.A Phase I study of 9-nitrocamptothecin given concurrently with capecitabine in patients with refractory, metastatic solid tumors.Cancer 2003 Jan 1;97(1):148-54.
  12491516
• Stokvis E, Rosing H, López-Lázaro L, Rodriguez I, Jimeno JM, Supko JG, Schellens JH, Beijnen JH.Quantitative analysis of the novel depsipeptide anticancer drug Kahalalide F in human plasma by high-performance liquid chromatography under basic conditions c
  12271442
• Eder JP, Supko JG, Clark JW, Puchalski TA, Garcia-Carbonero R, Ryan DP, Shulman LN, Proper J, Kirvan M, Rattner B, Connors S, Keogan MT, Janicek MJ, Fogler WE, Schnipper L, Kinchla N, Sidor C, Phillips E, Folkman J, Kufe DW.Phase I clinical trial of recom
  12228197
• Seiden MV, Ng SW, Supko JG, Ryan DP, Clark JW, Lynch T, Huang KC, Kwiatkowski D, Skarin A, Eder JP.A phase I clinical trial of sequentially administered doxorubicin and topotecan in refractory solid tumors.Clin Cancer Res 2002 Mar;8(3):691-7.
  11895897
• Garcia-Carbonero R, Supko JG.Current perspectives on the clinical experience, pharmacology, and continued development of the camptothecins.Clin Cancer Res 2002 Mar;8(3):641-61.
  11895891
• Bunnell CA, Supko JG, Eder JP, Clark JW, Lynch TJ, Kufe DW, Shulman LN.Phase I clinical trial of 7-cyanoquinocarcinol (DX-52-1) in adult patients with refractory solid malignancies.Cancer Chemother Pharmacol 2001 Nov;48(5):347-55.
  11761451
• Fidias P, Supko JG, Martins R, Boral A, Carey R, Grossbard M, Shapiro G, Ostler P, Lucca J, Johnson BE, Skarin A, Lynch TJ.A phase II study of weekly paclitaxel in elderly patients with advanced non-small cell lung cancer.Clin Cancer Res 2001 Dec;7(12):39
  11751486
• Supko JG, Garcia-Carbonero R, Puchalski TA, Malspeis L.Plasma pharmacokinetics and bioavailability of 1-(2-chloroethyl)-3-sarcosinamide-1-nitrosourea after intravenous and oral administration to mice and dogs.Cancer Chemother Pharmacol 2001 Sep;48(3):202-
  11592341
• Penson RT, Supko JG, Seiden MV, Fuller AF, Berkowitz RS, Goodman A, Campos SM, MacNeill KM, Cook S, Matulonis UA.A Phase I-II study of 96-hour infusional topotecan and paclitaxel for patients with recurrent Müllerian tumors.Cancer 2001 Sep 1;92(5):1156-67
  11571729
• Shapiro GI, Supko JG, Patterson A, Lynch C, Lucca J, Zacarola PF, Muzikansky A, Wright JJ, Lynch TJ, Rollins BJ.A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cance
  11410495
• Campos SM, Penson RT, Mays AR, Berkowitz RS, Fuller AF, Goodman A, Matulonis UA, Muzikansky A, Seiden MV.The clinical utility of liposomal doxorubicin in recurrent ovarian cancer.Gynecol Oncol 2001 May;81(2):206-12.
  11330951
• Ryan DP, Supko JG, Eder JP, Seiden MV, Demetri G, Lynch TJ, Fischman AJ, Davis J, Jimeno J, Clark JW.Phase I and pharmacokinetic study of ecteinascidin 743 administered as a 72-hour continuous intravenous infusion in patients with solid malignancies.Clin
  11234874
• Ciordia R, Supko J, Gatineau M, Batchelor T.Cytotoxic chemotherapy: advances in delivery, pharmacology, and testing.Curr Oncol Rep 2000 Sep;2(5):445-53.
  11122877
• Supko JG, Lynch TJ, Clark JW, Fram R, Allen LF, Velagapudi R, Kufe DW, Eder JP.A phase I clinical and pharmacokinetic study of the dolastatin analogue cemadotin administered as a 5-day continuous intravenous infusion.Cancer Chemother Pharmacol 2000;46(4):
  11052630
• Phillips LR, Malspeis L, Tubbs EK, Supko JG.Characterization of a novel degradation product of 2,2'-dithiobis[N-isoleucylbenzamide], an inhibitor of HIV nucleocapsid protein zinc fingers.J Pharm Biomed Anal 2000 Aug 15;23(2-3):395-402.
  10933532
• Supko JG, Nair RV, Seiden MV, Lu H.Adaptation of solid phase extraction to an automated column switching method for online sample cleanup as the basis of a facile and sensitive high-performance liquid chromatographic assay for paclitaxel in human plasma.J
  10703971
• Duska LR, Penson R, Supko JG, Finkelstein DM, Makastorsis T, Gallagher J, Borden K, Goodman A, Fuller AF, Nikrui N, Seiden MV.A Phase I study of continuous infusion doxorubicin and paclitaxel chemotherapy with granulocyte colony-stimulating factor for rel
  10389912
• Sharpless JL, Supko JG, Martin KA, Hall JE.Disappearance of endogenous luteinizing hormone is prolonged in postmenopausal women.J Clin Endocrinol Metab 1999 Feb;84(2):688-94.
  10022439
• Phillips LR, Wolfe TL, Malspeis L, Supko JG.Analysis of brefeldin A and the prodrug breflate in plasma by gas chromatography with mass selective detection.J Pharm Biomed Anal 1998 Apr;16(8):1301-9.
  9777604
• Supko JG, Soglia JR, Nair RV.Assay for the quinocarmycin analog DX-52-1 in human plasma using high-performance liquid chromatography with automated column switching and low wavelength ultraviolet detection.J Chromatogr B Biomed Sci Appl 1998 Sep 4;714(2):
  9766875
• Eder JP, Supko JG, Lynch T, Bryant M, Vosburgh E, Shulman LN, Xu G, Kufe DW.Phase I trial of the colloidal dispersion formulation of 9-amino-20(S)-camptothecin administered as a 72-hour continuous intravenous infusion.Clin Cancer Res 1998 Feb;4(2):317-24.
  9516917
• Eder JP, Rubin E, Stone R, Bryant M, Xu G, Supko J, Kinchla N, Lynch T, Hurwitz S, Rodriguez D, Shapiro C, Toppmeyer D, Grossbard M, Vosburg E, Huberman M, Schnipper L, Shulman L, Kufe DW.Trials of 9-amino-20(S)-camptothecin in Boston.Ann N Y Acad Sci 199
  8993518
• Supko JG, Phillips LR, Malspeis L.Specific high-performance liquid chromatographic assay with ultraviolet detection for the determination of 1-(2-chloroethyl)-3-sarcosinamide-1-nitrosourea in plasma.J Chromatogr B Biomed Appl 1996 Mar 3;677(2):351-62.
  8704941
• Rice WG, Supko JG, Malspeis L, Buckheit RW, Clanton D, Bu M, Graham L, Schaeffer CA, Turpin JA, Domagala J, Gogliotti R, Bader JP, Halliday SM, Coren L, Sowder RC, Arthur LO, Henderson LE.Inhibitors of HIV nucleocapsid protein zinc fingers as candidates f
  7502043
• Burger AM, Kaur G, Alley MC, Supko JG, Malspeis L, Grever MR, Sausville EA.Tyrphostin AG17, [(3,5-Di-tert-butyl-4-hydroxybenzylidene)- malononitrile], inhibits cell growth by disrupting mitochondria.Cancer Res 1995 Jul 1;55(13):2794-9.
  7796405
• Phillips LR, Malspeis L, Supko JG.Pharmacokinetics of active drug metabolites after oral administration of perillyl alcohol, an investigational antineoplastic agent, to the dog.Drug Metab Dispos 1995 Jul;23(7):676-80.
  7587953
• Supko JG, Phillips LR.High-performance liquid chromatographic assay for genistein in biological fluids.J Chromatogr B Biomed Appl 1995 Apr 7;666(1):157-67.
  7655614
• Supko JG, Malspeis L.Pharmacokinetics of michellamine B, a naphthylisoquinoline alkaloid with in vitro activity against human immunodeficiency virus types 1 and 2, in the mouse and dog.Antimicrob Agents Chemother 1995 Jan;39(1):9-14.
  7695336
• Supko JG, Hickman RL, Grever MR, Malspeis L.Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent.Cancer Chemother Pharmacol 1995;36(4):305-15.
  7628050
• Supko JG, Malspeis L.Determination of michellamine B in biological fluids by high-performance liquid chromatography with fluorescence detection.Anal Biochem 1994 Jan;216(1):52-60.
  8135366
• Supko JG, Malspeis L.Dose-dependent pharmacokinetics of rapamycin-28-N,N-dimethylglycinate in the mouse.Cancer Chemother Pharmacol 1994;33(4):325-30.
  8281627
• Supko JG, Balcerzak SP, Kraut EH.Phase I evaluation and pharmacokinetic study of pyrazine-2-diazohydroxide administered as a single bolus intravenous injection in patients with advanced solid tumors.Cancer Res 1993 Oct 15;53(20):4843-9.
  8402671
• Supko JG, Malspeis L.Pharmacokinetics of the 9-amino and 10,11-methylenedioxy derivatives of camptothecin in mice.Cancer Res 1993 Jul 1;53(13):3062-9.
  8319213
• Phillips LR, Supko JG, Malspeis L.Analysis of brefeldin A in plasma by gas chromatography with electron capture detection.Anal Biochem 1993 May 15;211(1):16-22.
  8323029
• Supko JG, Malspeis L.Liquid Chromatographic Analysis of 9-Aminocamptothecin in Plasma Monitored by Fluorescence Induced upon Postcolumn Acidification.Eval & Prog Plan 1992;15:3261-3283.
• Supko JG, Malspeis L.A Reversed-Phase HPLC Method for Determining Camptothecin in Plasma with Specificity for the Intact Lactone Form of the Drug.Eval & Prog Plan 1991;14:1779-1803.
• Supko JG, Malspeis L.Characterization of the urinary metabolites of merbarone in cancer patients.Drug Metab Dispos 1991 Jan-Feb;19(1):263-73.
  1673412