Howard Bailey, MD – UWCCC Director, and CPC Program Member
The Cancer Pharmacology Lab developed and validated an LC/MS/MS analytical assay for a first in human clinical trial of UAB30. UAB30 is a novel retinoid being developed as a chemoprevention agent and a therapeutic agent for breast cancer. The primary endpoint of this trial was to evaluate the single dose PK in normal volunteers, with the primary hypothesis that UAB30 would be orally available. This study demonstrated oral availability, dose proportionality as depicted below, primarily hepatic metabolism and a half-life of approximately eight hours for UAB30.
Means and Standard Error Bars of AUC and Cmax by UAB30 treatment group shown, along with fitted curves representing chosen models.
Glenn Liu, MD – Developmental Therapeutics Program
The Cancer Pharmacology Lab developed and validated an LC/MS/MS (liquid chromatography tandem mass spectrometry) assay for the analysis of sunitinib and performed an ELISA assay for VEGF, which were utilized in NCI #7898, “Pharmacodynamic Study Using FLT PET/CT in Patients with Renal Cell Cancer and Other Solid Malignancies Treated with Sunitinib Malate.”
Multivariate analysis demonstrated that plasma VEGF levels independently predict tumor proliferation during sunitinib treatment. PK and PD parameters at time points throughout the sunitinib cycle are shown. Thin dotted lines show individual patient results. (ccRCC, clear cell renal cell carcinoma.)
More about Cancer Pharmacology
Selected Publications
Funding received from the UWCCC Cancer Center Support Grant (CCSG) for published research, including the use of UWCCC Shared Resources to generate or analyze data, or conduct clinical trials, needs to reference the UWCCC. See Acknowledging UWCCC in Publications, Posters, and Presentations.
View the UW Drug Development Core (DDC) page for more information on other UW–Madison laboratory facilities that provide state-of-the-art instrumentation and expert scientific staff.
| Ramalingam SS, Lee JW, Belani CP, Aisner SC, Kolesar J, Howe C, Velasco MR, Schiller JH. Cetuximab for the treatment of advanced bronchioloalveolar carcinoma (BAC): an Eastern Cooperative Oncology Group phase II study (ECOG 1504). J Clin Oncol. 2011;29(13):1709-14. PMCID: PMC3107763. |
| Liu G, Jeraj R, Vanderhoek M, Perlman S, Kolesar J, Harrison M, Simoncic U, Eickhoff J, Carmichael L, Chao B, Marnocha R, Ivy P, Wilding G. Pharmacodynamic study using FLT PET/CT in patients with renal cell cancer and other solid malignancies treated with sunitinib malate. Clin Cancer Res. 2011;17(24):7634-44. PMCID: PMC3243764. |
| Dennie TW, Fleming RA, Bowen CJ, Dar MM, Alberti D, Oliver K, Loconte N, Mulkerin D, Holen KD. A phase I study of capecitabine, oxaliplatin, and lapatinib in metastatic or advanced solid tumors. Clin Colorectal Cancer. 2011;10(1):57-62. |
| Tevaarwerk A, Wilding G, Eickhoff J, Chappell R, Sidor C, Arnott J, Bailey H, Schelman W, Liu G. Phase I study of continuous MKC-1 in patients with advanced or metastatic solid malignancies using the modified Time-to-Event Continual Reassessment Method (TITE-CRM) dose escalation design. Invest New Drugs. 2011. PMCID: PMC3139017. |
| Cetnar J, Wilding G, McNeel D, Loconte NK, McFarland TA, Eickhoff J, Liu G. A phase 1/1b study of satraplatin (JM-216) in combination with docetaxel in patients with advanced solid tumors and metastatic castrate-resistant prostate cancer. Urol Oncol. 2011. |
| Kolesar JM, Sachidanandam K, Schelman WR, Eickhoff J, Holen KD, Traynor AM, Alberti DB, Thomas JP, Chitambar CR, Wilding G, Antholine WE. Cytotoxic Evaluation of 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone, 3-AP, in Peripheral Blood Lymphocytes of Patients with Refractory Solid Tumors using Electron Paramagnetic Resonance. Exp Ther Med. 2011;2(1):119-23. PMCID: PMC3046871. |
| Heath EI, Blumenschein GR, Jr., Cohen RB, Lorusso PM, Loconte NK, Kim ST, Ruiz-Garcia A, Chao RC, Wilding G. Sunitinib in combination with paclitaxel plus carboplatin in patients with advanced solid tumors: phase I study results. Cancer Chemother Pharmacol. 2011;68(3):703-12. |
| Kolesar J, Brundage RC, Pomplun M, Alberti D, Holen K, Traynor A, Ivy P, Wilding G. Population pharmacokinetics of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine(R)) in cancer patients. Cancer Chemother Pharmacol. 2011;67(2):393-400. PMCID: PMC3059107. |
| Rathkopf D, Liu G, Carducci MA, Eisenberger MA, Anand A, Morris MJ, Slovin SF, Sasaki Y, Takahashi S, Ozono S, Fung NK, Cheng S, Gan J, Gottardis M, Obermeier MT, Reddy J, Zhang S, Vakkalagadda BJ, Alland L, Wilding G, Scher HI, Prostate Cancer Clinical Trials C. Phase I dose-escalation study of the novel antiandrogen BMS-641988 in patients with castration-resistant prostate cancer. Clin Cancer Res. 2011;17(4):880-7. PMCID: PMC3070382. |
| Choi BS, Alberti DB, Schelman WR, Kolesar JM, Thomas JP, Marnocha R, Eickhoff JC, Ivy SP, Wilding G, Holen KD. The maximum tolerated dose and biologic effects of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) in combination with irinotecan for patients with refractory solid tumors. Cancer Chemother Pharmacol. 2010;66(5):973-80. PMCID: PMC2921466. |
| Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, Smith M, Anderson B, Villablanca JG, Matthay KK, Shimada H, Grupp SA, Seeger R, Reynolds CP, Buxton A, Reisfeld RA, Gillies SD, Cohn SL, Maris JM, Sondel PM, Children’s Oncology Group. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010;363(14):1324-34. PMCID: PMC3086629. |
| Wernimont SA, Simonson WT, Greer PA, Seroogy CM, Huttenlocher A. Calpain 4 is not necessary for LFA-1-mediated function in CD4+ T cells. PLoS One. 2010;5(5):e10513. PMCID: PMC2866319. |
| Wang J, Liu Y, Li Z, Du J, Ryu MJ, Taylor PR, Fleming MD, Young KH, Pitot H, Zhang J. Endogenous oncogenic Nras mutation promotes aberrant GM-CSF signaling in granulocytic/monocytic precursors in a murine model of chronic myelomonocytic leukemia. Blood. 2010;116(26):5991-6002. PMCID: PMC3031386. |
| Shusterman S, London WB, Gillies SD, Hank JA, Voss SD, Seeger RC, Reynolds CP, Kimball J, Albertini MR, Wagner B, Gan J, Eickhoff J, DeSantes KB, Cohn SL, Hecht T, Gadbaw B, Reisfeld RA, Maris JM, Sondel PM. Antitumor activity of hu14.18-IL2 in patients with relapsed/refractory neuroblastoma: a Children’s Oncology Group (COG) phase II study. J Clin Oncol. 2010;28(33):4969-75. PMCID: PMC3020698. |
| Lubner SJ, Mahoney MR, Kolesar JL, Loconte NK, Kim GP, Pitot HC, Philip PA, Picus J, Yong WP, Horvath L, Van Hazel G, Erlichman CE, Holen KD. Report of a multicenter phase II trial testing a combination of biweekly bevacizumab and daily erlotinib in patients with unresectable biliary cancer: a phase II Consortium study. J Clin Oncol. 2010;28(21):3491-7. PMCID: PMC2917213. |
| Kolesar JM, Hoel R, Pomplun M, Havighurst T, Stublaski J, Wollmer B, Krontiras H, Brouillette W, Muccio D, Kim K, Grubbs CJ, Bailey H. A pilot, first-in-human, pharmacokinetic study of 9cUAB30 in healthy volunteers. Cancer Prev Res. 2010;3(12):1565-70. PMCID: PMC3204611. |
| Harzstark AL, Rosenberg JE, Weinberg VK, Sharib J, Ryan CJ, Smith DC, Pagliaro LC, Beer TM, Liu G, Small EJ. Ixabepilone, mitoxantrone, and prednisone for metastatic castration-resistant prostate cancer after docetaxel-based therapy: a phase 2 study of the department of defense prostate cancer clinical trials consortium. Cancer. 2010. |
| Delgado DC, Hank JA, Kolesar J, Lorentzen D, Gan J, Seo S, Kim K, Shusterman S, Gillies SD, Reisfeld RA, Yang R, Gadbaw B, DeSantes KB, London WB, Seeger RC, Maris JM, Sondel PM. Genotypes of NK cell KIR receptors, their ligands, and Fcγ receptors in the response of neuroblastoma patients to Hu14.18-IL2 immunotherapy. Cancer Res. 2010;70(23):9554-61. PMCID: PMC2999644. |
| Bailey HH, Kim K, Verma AK, Sielaff K, Larson PO, Snow S, Lenaghan T, Viner JL, Douglas J, Dreckschmidt NE, Hamielec M, Pomplun M, Sharata HH, Puchalsky D, Berg ER, Havighurst TC, Carbone PP. A randomized, double-blind, placebo-controlled phase 3 skin cancer prevention study of {alpha}-difluoromethylornithine in subjects with previous history of skin cancer. Cancer Prev Res (Phila). 2010;3(1):35-47. PMCID: PMC2804946. |
| Tevaarwerk AJ, Holen KD, Alberti DB, Sidor C, Arnott J, Quon C, Wilding G, Liu G. Phase I trial of 2-methoxyestradiol NanoCrystal dispersion in advanced solid malignancies. Clin Cancer Res. 2009;15(4):1460-5. PMCID: PMC2892631. |
| Schelman WR, Morgan-Meadows S, Marnocha R, Lee F, Eickhoff J, Huang W, Pomplun M, Jiang Z, Alberti D, Kolesar JM, Ivy P, Wilding G, Traynor AM. A phase I study of Triapine in combination with doxorubicin in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2009;63(6):1147-56. PMCID: PMC3050713. |
| Kolesar J, Huang W, Eickhoff J, Hahn K, Alberti D, Attia S, Schelman W, Holen K, Traynor A, Ivy P, Wilding G. Evaluation of mRNA by Q-RTPCR and protein expression by AQUA of the M2 subunit of ribonucleotide reductase (RRM2) in human tumors. Cancer Chemother Pharmacol. 2009;64(1):79-86. PMCID: PMC3043989. |
| Hank JA, Gan J, Ryu H, Ostendorf A, Stauder MC, Sternberg A, Albertini M, Lo KM, Gillies SD, Eickhoff J, Sondel PM. Immunogenicity of the hu14.18-IL2 immunocytokine molecule in adults with melanoma and children with neuroblastoma. Clin Cancer Res. 2009;15(18):5923-30. PMCID: PMC2745522. |
| Bradley D, Rathkopf D, Dunn R, Stadler WM, Liu G, Smith DC, Pili R, Zwiebel J, Scher H, Hussain M. Vorinostat in advanced prostate cancer patients progressing on prior chemotherapy (National Cancer Institute Trial 6862): trial results and interleukin-6 analysis: a study by the Department of Defense Prostate Cancer Clinical Trial Consortium and University of Chicago Phase 2 Consortium. Cancer. 2009;115(23):5541-9. PMCID: PMC2917101. |
| Basu HS, Thompson TA, Church DR, Clower CC, Mehraein-Ghomi F, Amlong CA, Martin CT, Woster PM, Lindstrom MJ, Wilding G. A small molecule polyamine oxidase inhibitor blocks androgen-induced oxidative stress and delays prostate cancer progression in the transgenic adenocarcinoma of the mouse prostate model. Cancer Res. 2009;69(19):7689-95. PMCID: PMC2756327. |
| Argiris A, Buchanan A, Brockstein B, Kolesar J, Ghebremichael M, Pins M, Hahn K, Axelrod R, Forastiere A. Docetaxel and irinotecan in recurrent or metastatic head and neck cancer: a phase 2 trial of the Eastern Cooperative Oncology Group. Cancer. 2009;115(19):4504-13. PMCID: PMC2749918. |
| LoConte NK, Thomas JP, Alberti D, Heideman J, Binger K, Marnocha R, Utecht K, Geiger P, Eickhoff J, Wilding G, Kolesar J. A phase I pharmacodynamic trial of bortezomib in combination with doxorubicin in patients with advanced cancer. Cancer Chemother Pharmacol. 2008;63(1):109-15. |
| Attia S, Kolesar J, Mahoney MR, Pitot HC, Laheru D, Heun J, Huang W, Eickhoff J, Erlichman C, Holen KD. A phase 2 consortium (P2C) trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) for advanced adenocarcinoma of the pancreas. Invest New Drugs. 2008;26(4):369-79. |
| Ricart AD, Tolcher AW, Liu G, Holen K, Schwartz G, Albertini M, Weiss G, Yazji S, Ng C, Wilding G. Volociximab, a chimeric monoclonal antibody that specifically binds alpha5beta1 integrin: a phase I, pharmacokinetic, and biological correlative study. Clin Cancer Res. 2008;14(23):7924-9. NIHMSID: NIHMS340779 |
| Liu G, Kolesar J, McNeel DG, Leith C, Schell K, Eickhoff J, Lee F, Traynor A, Marnocha R, Alberti D, Zwiebel J, Wilding G. http://www.ncbi.nlm.nih.gov/pubmed/?term=PMC2950700 target=”_blank” Clin Cancer Res. 2008;14(9):2732-9. PMCID: PMC2950700. |
| Kolesar JM, Schelman WR, Geiger PG, Holen KD, Traynor AM, Alberti DB, Thomas JP, Chitambar CR, Wilding G, Antholine WE. Electron paramagnetic resonance study of peripheral blood mononuclear cells from patients with refractory solid tumors treated with Triapine. J Inorg Biochem. 2008;102(4):693-8. PMCID: PMC2390869. |
| Flaherty KT, Schiller J, Schuchter LM, Liu G, Tuveson DA, Redlinger M, Lathia C, Xia C, Petrenciuc O, Hingorani SR, Jacobetz MA, Van Belle PA, Elder D, Brose MS, Weber BL, Albertini MR, O’Dwyer PJ. A phase I trial of the oral, multikinase inhibitor sorafenib in combination with carboplatin and paclitaxel. Clin Cancer Res. 2008;14(15):4836-42. |
| Chaiswing L, Zhong W, Cullen JJ, Oberley LW, Oberley TD. Extracellular redox state regulates features associated with prostate cancer cell invasion. Cancer Res. 2008;68(14):5820-6. |
| Attia S, Eickhoff J, Wilding G, McNeel D, Blank J, Ahuja H, Jumonville A, Eastman M, Shevrin D, Glode M, Alberti D, Staab MJ, Horvath D, Straus J, Marnocha R, Liu G. Randomized, double-blinded phase II evaluation of docetaxel with or without doxercalciferol in patients with metastatic, androgen-independent prostate cancer. Clin Cancer Res. 2008;14(8):2437-43. |
| Takimoto CH, Graham MA, Lockwood G, Ng CM, Goetz A, Greenslade D, Remick SC, Sharma S, Mani S, Ramanathan RK, Synold TW, Doroshow JH, Hamilton A, Mulkerin DL, Ivy P, Egorin MJ, Grem JL. Oxaliplatin pharmacokinetics and pharmacodynamics in adult cancer patients with impaired renal function. Clin Cancer Res. 2007;13(16):4832-9. |
| Synold TW, Takimoto CH, Doroshow JH, Gandara D, Mani S, Remick SC, Mulkerin DL, Hamilton A, Sharma S, Ramanathan RK, Lenz HJ, Graham M, Longmate J, Kaufman BM, Ivy P, National Cancer Institute Organ Dysfunction Working Group study. Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: a National Cancer Institute Organ Dysfunction Working Group study. Clin Cancer Res. 2007;13(12):3660-6. |
| Zhang D, Pier T, McNeel DG, Wilding G, Friedl A. Effects of a monoclonal anti-alphavbeta3 integrin antibody on blood vessels – a pharmacodynamic study. Invest New Drugs. 2007;25(1):49-55. |
| MacKenzie DA, Schartner J, Lin J, Timmel A, Jennens-Clough M, Fathman CG, Seroogy CM. GRAIL is up-regulated in CD4+ CD25+ T regulatory cells and is sufficient for conversion of T cells to a regulatory phenotype. J Biol Chem. 2007;282(13):9696-702. |