Photo of Jeffrey G. Supko,  PhD

Jeffrey G. Supko, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 724-1970
Fax: (617) 726-6974

Jeffrey G. Supko, PhD

Massachusetts General Hospital


  • Associate Professor, Medicine, Harvard Medical School
  • Director, Clinical Pharmacology Laboratory, Massachusetts General Hospital



  • 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.


Powered by Harvard Catalyst
  • DeAngelo DJ, Stevenson KE, Dahlberg SE, Silverman LB, Couban S, Supko JG, Amrein PC, Ballen KK, Seftel MD, Turner AR, Leber B, Howson-Jan K, Kelly K, Cohen S, Matthews JH, Savoie L, Wadleigh M, Sirulnik LA, Galinsky I, Neuberg DS, Sallan SE, Stone RM. Long-term outcome of a pediatric-inspired regimen used for adults aged 18-50 years with newly diagnosed acute lymphoblastic leukemia. Leukemia 2015; 29:526-34. PubMed
  • Rosenfeld MR, Ye X, Supko JG, Desideri S, Grossman SA, Brem S, Mikkelson T, Wang D, Chang YC, Hu J, McAfee Q, Fisher J, Troxel AB, Piao S, Heitjan DF, Tan KS, Pontiggia L, O'Dwyer PJ, Davis LE, Amaravadi RK. A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. Autophagy 2014; 10:1359-68. PubMed
  • Wagle N, Grabiner BC, Van Allen EM, Hodis E, Jacobus S, Supko JG, Stewart M, Choueiri TK, Gandhi L, Cleary JM, Elfiky AA, Taplin ME, Stack EC, Signoretti S, Loda M, Shapiro GI, Sabatini DM, Lander ES, Gabriel SB, Kantoff PW, Garraway LA, Rosenberg JE. Activating mTOR mutations in a patient with an extraordinary response on a phase I trial of everolimus and pazopanib. 2014. PubMed
  • Goyal L, Supko JG, Berlin J, Blaszkowsky LS, Carpenter A, Heuman DM, Hilderbrand SL, Stuart KE, Cotler S, Senzer NN, Chan E, Berg CL, Clark JW, Hezel AF, Ryan DP, Zhu AX. Phase 1 study of N(1),N(11)窶租iethylnorspermine (DENSPM) in patients with advanced hepatocellular carcinoma. Cancer Chemother Pharmacol 2014; 72:1305-14. PubMed
  • Salzer WL, Asselin B, Supko JG, Devidas M, Kaiser NA, Plourde P, Winick NJ, Reaman GH, Raetz E, Carroll WL, Hunger SP. Erwinia asparaginase achieves therapeutic activity after pegaspargase allergy: a report from the Children's Oncology Group. Blood 2013; 122:507-14. PubMed
  • Brown JR, Messmer BT, Werner L, Davids MS, Mikler E, Supko JG, Fisher DC, Lacasce AS, Armand P, Jacobsen E, Dalton V, Tesar B, Fernandes SM, McDonough S, Ritz J, Rassenti L, Kipps TJ, Neuberg D, Freedman AS. A phase I study of escalated dose subcutaneous alemtuzumab given weekly with rituximab in relapsed chronic lymphocytic leukemia / small lymphocytic lymphoma. Haematologica 2013. PubMed
  • Wolpin BM, Ng K, Zhu AX, Abrams T, Enzinger PC, McCleary NJ, Schrag D, Kwak EL, Allen JN, Bhargava P, Chan JA, Goessling W, Blaszkowsky LS, Supko JG, Elliot M, Sato K, Regan E, Meyerhardt JA, Fuchs CS. Multicenter Phase II Study of Tivozanib (AV-951) and Everolimus (RAD001) for Patients With Refractory, Metastatic Colorectal Cancer. Oncologist 2013. PubMed
  • Holkova B, Supko JG, Ames MM, Reid JM, Shapiro GI, Perkins EB, Ramakrishnan V, Tombes MB, Honeycutt C, McGovern RM, Kmieciak M, Shrader E, Wellons MD, Sankala H, Doyle A, Wright J, Roberts JD, Grant S. A phase I trial of vorinostat and alvocidib in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2. Clin Cancer Res 2013; 19:1873-83. PubMed
  • Peereboom DM, Ahluwalia MS, Ye X, Supko JG, Hilderbrand SL, Phuphanich S, Nabors LB, Rosenfeld MR, Mikkelsen T, Grossman SA, . NABTT 0502: a phase II and pharmacokinetic study of erlotinib and sorafenib for patients with progressive or recurrent glioblastoma multiforme. 2013; 15:490-6. PubMed
  • Vrooman LM, Stevenson KE, Supko JG, O'Brien J, Dahlberg SE, Asselin BL, Athale UH, Clavell LA, Kelly KM, Kutok JL, Laverdière C, Lipshultz SE, Michon B, Schorin M, Relling MV, Cohen HJ, Neuberg DS, Sallan SE, Silverman LB. Postinduction dexamethasone and individualized dosing of Escherichia Coli L-asparaginase each improve outcome of children and adolescents with newly diagnosed acute lymphoblastic leukemia: results from a randomized study--Dana-Farber Cancer Institute ALL J Clin Oncol 2013; 31:1202-10. PubMed
  • Zhu AX, Ancukiewicz M, Supko JG, Sahani DV, Blaszkowsky LS, Meyerhardt JA, Abrams TA, McCleary NJ, Bhargava P, Muzikansky A, Sheehan S, Regan E, Vasudev E, Knowles M, Fuchs CS, Ryan DP, Jain RK, Duda DG. Efficacy, safety, pharmacokinetics, and biomarkers of cediranib monotherapy in advanced hepatocellular carcinoma: a phase II study. Clin Cancer Res 2013; 19:1557-66. PubMed
  • Hu J, Wen PY, Abrey LE, Fadul CE, Drappatz J, Salem N, Supko JG, Hochberg F. A phase II trial of oral gimatecan for recurrent glioblastoma. J. Neurooncol. 2013; 111:347-53. PubMed
  • Goldberg SB, Supko JG, Neal JW, Muzikansky A, Digumarthy S, Fidias P, Temel JS, Heist RS, Shaw AT, McCarthy PO, Lynch TJ, Sharma S, Settleman JE, Sequist LV. A phase I study of erlotinib and hydroxychloroquine in advanced non-small-cell lung cancer. J Thorac Oncol 2012; 7:1602-8. PubMed
  • Chen L, Aktas BH, Wang Y, He X, Sahoo R, Zhang N, Denoyelle S, Kabha E, Yang H, Freedman RY, Supko JG, Chorev M, Wagner G, Halperin JA. Tumor suppression by small molecule inhibitors of translation initiation. 2012; 3:869-81. PubMed
  • Hong DS, Kurzrock R, Supko JG, He X, Naing A, Wheler J, Lawrence D, Eder JP, Meyer CJ, Ferguson DA, Mier J, Konopleva M, Konoplev S, Andreeff M, Kufe D, Lazarus H, Shapiro GI, Dezube BJ. A phase i first-in-human trial of bardoxolone methyl in patients with advanced solid tumors and lymphomas. Clin Cancer Res 2012; 18:3396-406. PubMed
  • Raina D, Kosugi M, Ahmad R, Panchamoorthy G, Rajabi H, Alam M, Shimamura T, Shapiro GI, Supko JG, Kharbanda S, Kufe DW. DEPENDENCE ON THE MUC1-C ONCOPROTEIN IN NON-SMALL CELL LUNG CANCER CELLS WITH EGFR AND K-RAS MUTATIONS. Mol Cancer Ther 2011. PubMed
  • Peereboom DM, Supko JG, Carson KA, Batchelor T, Phuphanich S, Lesser G, Mikkelson T, Fisher J, Desideri S, He X, Grossman SA, . A phase I/II trial and pharmacokinetic study of ixabepilone in adult patients with recurrent high-grade gliomas. J. Neurooncol. 2010; 100:261-8. PubMed
  • Phuphanich S, Supko JG, Carson KA, Grossman SA, Burt Nabors L, Mikkelsen T, Lesser G, Rosenfeld S, Desideri S, Olson JJ. Phase 1 clinical trial of bortezomib in adults with recurrent malignant glioma. J. Neurooncol. 2010; 100:95-103. PubMed
  • Bird GH, Madani N, Perry AF, Princiotto AM, Supko JG, He X, Gavathiotis E, Sodroski JG, Walensky LD. Hydrocarbon double-stapling remedies the proteolytic instability of a lengthy peptide therapeutic. Proc Natl Acad Sci U S A 2010; 107:14093-8. PubMed
  • Peereboom DM, Supko JG, Carson KA, Batchelor T, Phuphanich S, Lesser G, Mikkelsen T, Fisher J, Desideri S, He X, Grossman SA, . Erratum to: A phase I/II trial and pharmacokinetic study of ixabepilone in adult patients with recurrent high-grade gliomas. J. Neurooncol. 2010. PubMed
  • Holdhoff M, Supko JG, Gallia GL, Hann CL, Bonekamp D, Ye X, Cao B, Olivi A, Grossman SA. Intratumoral concentrations of imatinib after oral administration in patients with glioblastoma multiforme. J. Neurooncol. 2010; 97:241-5. PubMed
  • Silverman LB, Supko JG, Stevenson KE, Woodward C, Vrooman LM, Neuberg DS, Asselin BL, Athale UH, Clavell L, Cole PD, Kelly KM, Laverdière C, Michon B, Schorin M, Schwartz CL, O'Brien JE, Cohen HJ, Sallan SE. Intravenous PEG-asparaginase during remission induction in children and adolescents with newly diagnosed acute lymphoblastic leukemia. Blood 2010; 115:1351-3. PubMed
  • Vrooman LM, Supko JG, Neuberg DS, Asselin BL, Athale UH, Clavell L, Kelly KM, Laverdière C, Michon B, Schorin M, Cohen HJ, Sallan SE, Silverman LB. Erwinia asparaginase after allergy to E. coli asparaginase in children with acute lymphoblastic leukemia. Pediatr Blood Cancer 2009; 54:199-205. PubMed
  • Fidias P, Pennell NA, Boral AL, Shapiro GI, Skarin AT, Eder JP, Kwoh TJ, Geary RS, Johnson BE, Lynch TJ, Supko JG. Phase I study of the c-raf-1 antisense oligonucleotide ISIS 5132 in combination with carboplatin and paclitaxel in patients with previously untreated, advanced non-small cell lung cancer. J Thorac Oncol 2009; 4:1156-62. PubMed
  • Kieran MW,Supko JG,Wallace D,Fruscio R,Poussaint TY,Phillips P,Pollack I,Packer R,Boyett JM,Blaney S,Banerjee A,Geyer R,Friedman H,Goldman S,Kun LE,Macdonald T. Phase I study of SU5416, a small molecule inhibitor of the vascular endothelial growth factor receptor (VEGFR) in refractory pediatric central nervous system tumors. Pediatr Blood Cancer 2008; 52:169-76. PubMed
  • Blakeley JO,Olson J,Grossman SA,He X,Weingart J,Supko JG. Effect of blood brain barrier permeability in recurrent high grade gliomas on the intratumoral pharmacokinetics of methotrexate: a microdialysis study. J Neurooncol 2008; 91:51-8. PubMed
  • Zhu AX,Ready N,Clark JW,Safran H,Amato A,Salem N,Pace S,He X,Zvereva N,Lynch TJ,Ryan DP,Supko JG. Phase I and pharmacokinetic study of gimatecan given orally once a week for 3 of 4 weeks in patients with advanced solid tumors. Clin Cancer Res 2009; 15:374-81. PubMed
  • Grossman SA,Carson KA,Phuphanich S,Batchelor T,Peereboom D,Nabors LB,Lesser G,Hausheer F,Supko JG. Phase I and pharmacokinetic study of karenitecin in patients with recurrent malignant gliomas. Neuro-oncol 2008; 10:608-16. PubMed
  • Miao XS,Song P,Savage RE,Zhong C,Yang RY,Kizer D,Wu H,Volckova E,Ashwell MA,Supko JG,He X,Chan TC. Identification of the in vitro metabolites of 3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione (ARQ 501; beta-lapachone) in whole blood. Drug Metab Dispos 2008; 36:641-8. PubMed
  • 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; 10:190-8. PubMed
  • 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 idarubicin and cytarabine in patients with acute myelogenous leukemia. Clin Cancer Res 2008; 14:1446-54. PubMed
  • 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, Settleman J. Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling. Proc Natl Acad Sci U S A 2007; 104:19936-41. PubMed
  • 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 with metastatic colorectal cancer. Cancer Chemother Pharmacol 2007; 60:661-70. PubMed
  • Akingbemi BT,Braden TD,Kemppainen BW,Hancock KD,Sherrill JD,Cook SJ,He X,Supko JG. Exposure to phytoestrogens in the perinatal period affects androgen secretion by testicular Leydig cells in the adult rat. Endocrinology 2007; 148:4475-88. PubMed
  • Srouji SS, Pagán YL, D'Amato F, Dabela A, Jimenez Y, Supko JG, Hall JE. Pharmacokinetic factors contribute to the inverse relationship between luteinizing hormone and body mass index in polycystic ovarian syndrome. J Clin Endocrinol Metab 2007; 92:1347-52. PubMed
  • 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; 13:584-90. PubMed
  • 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; 107:2688-97. PubMed
  • 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; 107:2482-9. PubMed
  • 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; 12:5174-81. PubMed
  • 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; 354:1615-25. PubMed
  • 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; 100:205-9. PubMed
  • 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 amifostine in patients with advanced head and neck carcinoma. Cancer 2005; 104:1418-27. PubMed
  • 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 2004; 113:490-8. PubMed
  • 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 of non-small-cell lung cancer to gefitinib. N Engl J Med 2004; 350:2129-39. PubMed