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Genomes and GenesSpecies | M J RatainSummaryAffiliation: University of Chicago Country: USA Publications
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Individualizing dosing of irinotecanMark J Ratain
Section of Hematology Oncology, Department of Medicine, Committee on Clinical Pharmacology and Pharmacogenomics, and Cancer Research Center, The University of Chicago, Chicago, Illinois 60637, USA
Clin Cancer Res 16:371-2. 2010..Irinotecan is an interesting agent for individualized dosing, given its complex metabolism and increasing knowledge of its pharmacokinetics predictors...
Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinomaMark J Ratain
University of Chicago, Chicago, IL 60637, USA
J Clin Oncol 24:2505-12. 2006..This phase II randomized discontinuation trial evaluated the effects of sorafenib (BAY 43-9006), an oral multikinase inhibitor targeting the tumor and vasculature, on tumor growth in patients with metastatic renal cell carcinoma...
Optimising the design of phase II oncology trials: the importance of randomisationMark J Ratain
Section of Hematology Oncology, Department of Medicine, Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, IL, USA
Eur J Cancer 45:275-80. 2009....
From bedside to bench to bedside to clinical practice: an odyssey with irinotecanMark J Ratain
Section of Hematology/Oncology, Department of Medicine, Committees on Clinical Pharmacology and Pharmacogenomics and Molecular Medicine, and Cancer Research Center, The University of Chicago, Chicago, Illinois 60637, USA
Clin Cancer Res 12:1658-60. 2006
Merrill Jon Egorin, MD, 1948-2010M J Ratain
Department of Medicine, University of Chicago, Chicago, Illinois, USA
Clin Pharmacol Ther 89:163-5. 2011..He is remembered as a compassionate physician, an outstanding scientist, an entertaining lecturer, a superb mentor, and a friend to many...
Personalized medicine: building the GPS to take us thereM J Ratain
Section of Hematology/Oncology, Department of Medicine, Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, Illinois, USA
Clin Pharmacol Ther 81:321-2. 2007
Recommended changes to oncology clinical trial design: revolution or evolution?Mark J Ratain
University of Chicago, Chicago, IL, USA
Eur J Cancer 44:8-11. 2008
The cancer and leukemia group B pharmacology and experimental therapeutics committee: a historical perspectiveMark J Ratain
University of Chicago, Chicago, Illinois, USA
Clin Cancer Res 12:3612s-6s. 2006..It is anticipated that the results of the current studies will contribute significantly to the goal of individualizing cancer treatment...
Phase I study to evaluate multiple regimens of intravenous 5-fluorouracil administered in combination with weekly gemcitabine in patients with advanced solid tumors: a potential broadly active regimen for advanced solid tumor malignanciesS Mani
University of Chicago Medical Center, Section of Hematology Oncology, Chicago, Illinois, USA
Cancer 92:1567-76. 2001..The purpose of this study was to determine the maximum tolerated dose and toxicity profile of gemcitabine given on a weekly schedule with continuous infusion 5-fluorouracil...
Phenotype-genotype correlation of in vitro SN-38 (active metabolite of irinotecan) and bilirubin glucuronidation in human liver tissue with UGT1A1 promoter polymorphismL Iyer
Department of Human Genetics, Cancer Research Center, University of Chicago, IL 60637, USA
Clin Pharmacol Ther 65:576-82. 1999..The presence of an additional TA repeat [(TA)7TAA] in the TATA sequence of UGT1A1 has been associated with Gilbert's syndrome...
Phase I study of ZD9331 on short daily intravenous bolus infusion for 5 days every 3 weeks with fixed dosing recommendationsB C Goh
Section of Hematology/Oncology, Cancer Research Center, University of Chicago, Chicago, IL, USA
J Clin Oncol 19:1476-84. 2001..CONCLUSION: The recommended dose for ZD9331 on this schedule is 25 mg/d. Neutropenia, thrombocytopenia, and rash were dose-limiting, and efficacy studies in colorectal cancer are indicated...
A phase I study of sirolimus and bevacizumab in patients with advanced malignanciesE E W Cohen
Section of Hematology and Oncology, Department of Medicine, Comprehensive Cancer Center, Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, IL, USA
Eur J Cancer 47:1484-9. 2011..We performed a single institution, phase I study of sirolimus and bevacizumab, in order to determine the dose limiting toxicity (DLT) and recommended phase II doses...
Phase I clinical and pharmacogenetic study of weekly TAS-103 in patients with advanced cancerR B Ewesuedo
Committee on Clinical Pharmacology, Section of Pediatric Hematology-Oncology, Department of Pediatrics, University of Chicago, IL 60637, USA
J Clin Oncol 19:2084-90. 2001..Further studies to characterize the pharmacodynamics and pharmacogenetics of TAS-103 are warranted...
Phase I clinical and pharmacologic study of eniluracil plus fluorouracil in patients with advanced cancerR L Schilsky
University of Chicago Cancer Research Center and the University of Chicago Committee on Clinical Pharmacology, IL 60637, USA
J Clin Oncol 16:1450-7. 1998....
A phase I study of the oral combination of CI-994, a putative histone deacetylase inhibitor, and capecitabineS D Undevia
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA
Ann Oncol 15:1705-11. 2004..CONCLUSIONS: The recommended phase II dose is 6 mg/m2 (or 10 mg) of CI-994 in combination with capecitabine 2000 mg/m2/day for 2 weeks of a 3-week cycle...
O6-benzylguanine in humans: metabolic, pharmacokinetic, and pharmacodynamic findingsM E Dolan
Section of Hematology Oncology, Cancer Research Center and Committee on Clinical Pharmacology, The University of Chicago, IL 60637, USA
J Clin Oncol 16:1803-10. 1998..The objective of this study was to determine the pharmacokinetics and metabolic fate of O6-Benzylguanine in humans and its effect on AGT activity in peripheral-blood mononuclear cells (PBMCs)...
Phase I clinical and pharmacological study of O6-benzylguanine followed by carmustine in patients with advanced cancerR L Schilsky
Department of Medicine, Cancer Research Center and Committee on Clinical Pharmacology, University of Chicago, Illinois 60637, USA
Clin Cancer Res 6:3025-31. 2000..Bone marrow suppression, which may be cumulative, is the dose-limiting toxicity of the combination. Prolonged AGT suppression is likely attributable primarily to the effect of O6-benzyl-8-oxoguanine...
The UGT1A1*28 polymorphism correlates with erlotinib's effect on SN-38 glucuronidationYong Liu
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
Eur J Cancer 46:2097-103. 2010..UGT1A1*28 polymorphism correlates with erlotinib's effect on SN-38 glucuronidation. The present findings shed light on the development and optimisation of combinations involving irinotecan and erlotinib...
Lack of association between common polymorphisms in UGT1A9 and gene expression and activityJacqueline Ramirez
Department of Medicine, University of Chicago, Chicago, IL 60637, USA
Drug Metab Dispos 35:2149-53. 2007..Our data demonstrate that the common I399C>T and-118T(9>10) polymorphisms do not explain interindividual variation in hepatic UGT1A9 activity and mRNA expression and are in complete LD in the donor liver samples we studied...
UGT1A1*28 genotype affects the in-vitro glucuronidation of thyroxine in human liversAndrea L Yoder Graber
Department of Medicine, University of Chicago, Chicago, IL 60637, USA
Pharmacogenet Genomics 17:619-27. 2007..The aims of this study were to determine the T4 glucuronidation ability of all commercially available human UGTs, and investigate the relationship between genetic polymorphisms in UGT1A1 and UGT1A9 and T4 glucuronidation in human livers...
A phase I trial of pharmacologic modulation of irinotecan with cyclosporine and phenobarbitalFederico Innocenti
Department of Medicine, Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, IL 60637, USA
Clin Pharmacol Ther 76:490-502. 2004..Five partial responses were observed. Pharmacokinetic modulation of irinotecan with cyclosporine and phenobarbital has been demonstrated; further studies are necessary to evaluate whether this strategy improves the therapeutic index...
Design of phase II cancer trials using a continuous endpoint of change in tumor size: application to a study of sorafenib and erlotinib in non small-cell lung cancerTheodore G Karrison
Department of Health Studies, University of Chicago, Chicago, IL 60637, USA
J Natl Cancer Inst 99:1455-61. 2007..This design may efficiently eliminate truly ineffective therapy but may not reliably indicate whether subsequent phase III testing is warranted...
A comparison of the pharmacokinetics and pharmacodynamics of docetaxel between African-American and Caucasian cancer patients: CALGB 9871Lionel D Lewis
Sections of Clinical Pharmacology and Hematology Oncology, Department of Medicine, Dartmouth Medical School, The Norris Cotton Cancer Center, Lebanon, New Hampshire 03756, USA
Clin Cancer Res 13:3302-11. 2007..We hypothesized that the pharmacokinetics and pharmacodynamics of docetaxel, an i.v. administered cytotoxic and substrate for CYP3A4, CYP3A5, and ABCB1, would differ between African-American and Caucasian patients...
Pharmacogenetics and pharmacogenomics of anticancer agentsR Stephanie Huang
Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
CA Cancer J Clin 59:42-55. 2009....
Study of cohort-specific consent and patient control in phase I cancer trialsC K Daugherty
Department of Medicine, The MacLean Center for Clinical Medical Ethics, University of Chicago, IL 60637 1470, USA
J Clin Oncol 16:2305-12. 1998....
Pharmacogenetics of anticancer agents: lessons from amonafide and irinotecanF Innocenti
Committee on Clinical Pharmacology, The University of Chicago, Illinois 60637, USA
Drug Metab Dispos 29:596-600. 2001..A clinical trial at the University of Chicago is ongoing to demonstrate the predictive significance of UGT1A1 genotyping for irinotecan pharmacodynamics...
Body surface area as a determinant of pharmacokinetics and drug dosingM Sawyer
Committee on Clinical Pharmacology, Department of Medicine, and Cancer Research Center, The University of Chicago, 60637-1470, IL, USA
Invest New Drugs 19:171-7. 2001..Future clinical trials of new agents should not presume that dosing based on BSA reduces interpatient variability. Studies should examine the role, if any, BSA has in dosing new chemotherapeutic agents in initial phase I studies...
Phase I Trial of ISIS 5132, an antisense oligonucleotide inhibitor of c-raf-1, administered by 24-hour weekly infusion to patients with advanced cancerC M Rudin
Section of Hematology Oncology, University of Chicago Medical Center, Chicago, Illinois 60637 1470, USA
Clin Cancer Res 7:1214-20. 2001....
Dynamic contrast-enhanced magnetic resonance imaging pharmacodynamic biomarker study of sorafenib in metastatic renal carcinomaOlwen M Hahn
University of Chicago, Chicago, IL 60637, USA
J Clin Oncol 26:4572-8. 2008..Sorafenib is an antiangiogenic agent with activity in renal cancer. We conducted a randomized trial to investigate dynamic contrast magnetic resonance imaging (DCE-MRI) as a pharmacodynamic biomarker...
Pharmacogenomics: road to anticancer therapeutics nirvana?Apurva A Desai
Department of Medicine, The University of Chicago, Chicago, IL, USA
Oncogene 22:6621-8. 2003..This review discusses the role of genetic variants of UGT1A1, TS and EGFR to exemplify the potential impact of phramacogenomics on the field of anticancer therapeutics...
Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecanFederico Innocenti
Department of Medicine, University of Chicago, 5841 S Maryland Ave, MC2115, Chicago, IL 60637, USA
J Clin Oncol 22:1382-8. 2004..UDP-glucuronosyltransferase 1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38. This study prospectively evaluated the association between the prevalence of severe toxicity and UGT1A1 genetic variation...
Pharmacokinetic modulation of oral etoposide by ketoconazole in patients with advanced cancerWei Peng Yong
Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, 5841 S Maryland Ave, MC2115, Chicago, IL 60637, USA
Cancer Chemother Pharmacol 60:811-9. 2007..Hence, this study was designed to evaluate if pharmacokinetic modulation of oral etoposide with ketoconazole could lead to a favorable alteration of etoposide pharmacokinetics, and to assess the feasibility and safety of this approach...
Phase I study of an oral formulation of ZD9331 administered daily for 28 daysMichael B Sawyer
Committe on Clinical Pharmacology, Department of Medicine, Cancer Research Center and Section of Hematology/Oncology, University of Chicago, IL USA
J Clin Oncol 21:1859-65. 2003..ZD9331 seems to have a manageable toxicity profile, although it should be used with caution in patients with renal impairment...
Phase 1 dose escalation study of docetaxel with filgrastim support in patients with advanced solid tumorsGregory A Masters
Feinberg School of Medicine of Northwestern University, Evanston Northwestern Healthcare, Evanston, IL, USA
Med Oncol 20:7-12. 2003..The docetaxel dose can be safely escalated to 145 mg/m(2) every 21 d with GCSF support, a 45% increase above the standard recommended phase II dose. Further studies will clarify the role of dose-intensified docetaxel...
Haplotype structure of the UDP-glucuronosyltransferase 1A1 promoter in different ethnic groupsFederico Innocenti
Department of Medicine, Committee on Clinical Pharmacology and Pharmacogenomics, Cancer Research Center, The University of Chicago, Chicago, IL 60637, USA
Pharmacogenetics 12:725-33. 2002..This study showed that (i) common promoter variants are in linkage disequilibrium and (ii) the haplotype structure of promoter is probably different between Caucasians and African-Americans...
A phase I study of antisense oligonucleotide GTI-2040 given by continuous intravenous infusion in patients with advanced solid tumorsA A Desai
Section of Hematology and Oncology, University of Chicago, Chicago, IL 60637, USA
Ann Oncol 16:958-65. 2005..CONCLUSIONS: The recommended dose of GTI-2040 given on this infusion schedule is 185 mg/m(2)/day. GTI-2040 appears to have a manageable toxicity profile and is generally well tolerated as a single agent...
A dosing/cross-development study of the multikinase inhibitor sorafenib in patients with pulmonary arterial hypertensionM Gomberg-Maitland
Section of Cardiology, Department of Medicine, University of Chicago, Chicago, Illinois, USA
Clin Pharmacol Ther 87:303-10. 2010..The most common adverse events were moderate skin reactions on the hands and feet and alopecia. Our conclusion was therefore that this is a tolerable dosing regimen for testing the therapeutic activity of sorafenib in PAH patients...
Epirubicin glucuronidation is catalyzed by human UDP-glucuronosyltransferase 2B7F Innocenti
The University of Chicago, Department of Medicine, Chicago, IL 60637, USA
Drug Metab Dispos 29:686-92. 2001..The reported tyrosine to histidine polymorphism in UGT2B7 does not alter the formation rate of epirubicin glucuronide, and undiscovered genetic polymorphisms in UGT2B7 might change the metabolic fate of this important anticancer agent...
UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicityL Iyer
Department of Medicine, The University of Chicago, IL, USA
Pharmacogenomics J 2:43-7. 2002..The results suggest that screening for UGT1A1*28 polymorphism may identify patients with lower SN-38 glucuronidation rates and greater susceptibility to irinotecan induced gastrointestinal and bone marrow toxicity...
Hepatocyte nuclear factor-1 alpha is associated with UGT1A1, UGT1A9 and UGT2B7 mRNA expression in human liverJ Ramirez
Department of Medicine, University of Chicago, Chicago, IL 60637, USA
Pharmacogenomics J 8:152-61. 2008..However, the amount of UGT intergenotype variability explained by HNF1alpha expression appears to be modest, and further studies should investigate the role of multiple transcription factors...
Pharmacogenetics in cancer treatmentR Nagasubramanian
Department of Pediatrics, University of Chicago, Chicago, Illinois 60637, USA
Annu Rev Med 54:437-52. 2003..Finally, the potential implications of transporter pharmacogenetics in influencing drug bioavailability are addressed...
Phase I study of the combination of losoxantrone and cyclophosphamide in patients with refractory solid tumoursB C Goh
Department of Medicine, Section of Hematology Oncology, University of Chicago, 5841 S Maryland Avenue, Illinois, IL 60637, USA
Br J Cancer 86:534-9. 2002..The recommended dose for further testing is cyclophosphamide 500 mg m(-2) followed by losoxantrone 95 mg m(-2) with granulocyte colony-stimulating factor support...
Phase I clinical and pharmacokinetic study of protein kinase C-alpha antisense oligonucleotide ISIS 3521 administered in combination with 5-fluorouracil and leucovorin in patients with advanced cancerSridhar Mani
Department of Medicine, Section of Hematology Oncology, Cancer Research Center, University of Chicago, Chicago, Illinois 60637, USA
Clin Cancer Res 8:1042-8. 2002..Our study warrants further exploration of efficacy in a Phase II and/or Phase III clinical trial setting...
Haplotypes of variants in the UDP-glucuronosyltransferase1A9 and 1A1 genesFederico Innocenti
Department of Medicine, University of Chicago, Chicago, IL, USA
Pharmacogenet Genomics 15:295-301. 2005..SN-38, the active metabolite of the anticancer agent irinotecan, is metabolized by both UGT1A1 and UGT1A9. We aim to characterize the UGT1A9-UGT1A1 haplotypes in Asians and Caucasians and gain insights on their functional consequences...
The role of pharmacogenetics in cancer therapeuticsWei Peng Yong
University of Chicago, Committee on Clinical Pharmacology and Pharmacogenomics, Department of Medicine and Cancer Research Center, Chicago, IL 60637, USA
Br J Clin Pharmacol 62:35-46. 2006....
A pharmacogenetic study of uridine diphosphate-glucuronosyltransferase 2B7 in patients receiving morphineMichael B Sawyer
Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, IL, USA
Clin Pharmacol Ther 73:566-74. 2003..045 and P =.004, respectively). Interindividual differences in morphine glucuronidation may be the result of genetic variation in UGT2B7, and further studies are indicated...
Study of the genetic determinants of UGT1A1 inducibility by phenobarbital in cultured human hepatocytesJacqueline Ramirez
Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA
Pharmacogenet Genomics 16:79-86. 2006..The indel at -53 affects the basal phenotype and appears to limit the hepatocyte capability of maximal induction after phenobarbital. However, variants at -53, -3156 and -3279 are not associated with variability in UGT1A1 inducibility...
Estimation of renal cell carcinoma treatment effects from disease progression modelingM L Maitland
Section of Hematology Oncology, Department of Medicine, University of Chicago, Chicago, Illinois, USA
Clin Pharmacol Ther 93:345-51. 2013..1) with 50 patients per arm. Model-based quantitation of treatment effect with computed tomography (CT) imaging offers a scaffold on which to develop new, more efficient, phase II trial end points and analytic strategies for RCC...
Phase I study of concomitant chemoradiotherapy with paclitaxel, fluorouracil, and hydroxyurea with granulocyte colony-stimulating factor support for patients with poor-prognosis cancer of the head and neckB Brockstein
Section of Hematology Oncology, University of Chicago Department of Medicine, IL, USA
J Clin Oncol 16:735-44. 1998..In the trial reported here, we added paclitaxel to the FHX base and used hyperfractionated RT to determine the maximum-tolerated dose (MTD), toxicities, and response rate in a poor-prognosis group of patients...
Phase II trial of paclitaxel and topotecan with granulocyte colony-stimulating factor support in stage IV breast cancerG F Fleming
Section of Hematology Oncology, University of Chicago, The University of Chicago Phase II Cooperative Network, Chicago, IL 60637 1470, USA
J Clin Oncol 16:2032-7. 1998..Plasma levels of paclitaxel and topotecan were obtained during cycle 1 to correlate pharmacokinetic parameters with toxicity...
Inflammation of actinic keratoses subsequent to therapy with sorafenib, a multitargeted tyrosine-kinase inhibitorM E Lacouture
Section of Dermatology, Department of Medicine, University of Chicago, IL, USA
Clin Exp Dermatol 31:783-5. 2006..This side-effect is of clinical importance, as early recognition is critical for early treatment and may represent a source of additional morbidity to these patients...
Nonprofit biomedical companiesR M Conti
Department of Pediatrics, Section of Pediatric Hematology Oncology, Center on Health and the Social Sciences, Program on Pharmaceutical Policy, Cancer Research Center, The University of Chicago, Chicago, Illinois, USA
Clin Pharmacol Ther 84:194-7. 2008..We conclude with a suggestion that opportunities exist for nonprofit firms focused on cancer diagnostics, given the limitations of current financing incentives and ripe scientific opportunity...
Phase II and pharmacodynamic studies of pyrazine diazohydroxide (NSC 361456) in patients with advanced renal and colorectal cancerN J Vogelzang
Cancer Research Center, University of Chicago Pritzker School of Medicine, Illinois 60637 1470, USA
Clin Cancer Res 4:929-34. 1998..Curiously, an increase in alkaline phosphatase was associated with an increase in the platelet nadir (P = 0.02). If PZDH continues to be developed as an antineoplastic agent, further studies of these relationships are suggested...
TPMT, UGT1A1 and DPYD: genotyping to ensure safer cancer therapy?Michael L Maitland
Department of Medicine, Committee on Clinical Pharmacology and Pharmacogenomics, and Cancer Research Center, University of Chicago, Chicago, IL 60637, USA
Trends Pharmacol Sci 27:432-7. 2006....
Pharmacogenetics of irinotecan: clinical perspectives on the utility of genotypingFederico Innocenti
The University of Chicago, Committee on Clinical Pharmacology and Pharmacogenomics, Chicago, IL, USA
Pharmacogenomics 7:1211-21. 2006....
A Phase II trial of suramin monthly x 3 for hormone-refractory prostate carcinomaNicholas J Vogelzang
Section of Hematology Oncology, Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA
Cancer 100:65-71. 2004....
R(+)XK469 inhibits hydroxylation of S-warfarin by CYP2C9Wei Peng Yong
Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, IL 60637, USA
Eur J Cancer 45:1904-8. 2009..We report eight subjects who experienced significant elevation of INR while receiving concomitant R(+)XK469 and warfarin. The aim of the study is to investigate whether R(+)XK469 interacts with S-warfarin by inhibition of CYP2C9...
Attitudes toward research participation and investigator conflicts of interest among advanced cancer patients participating in early phase clinical trialsStacy W Gray
Section of Hematology, Cancer Research Center, Committee on Clinical Pharmacology and Pharmacogenomics, MacLean Center for Clinical Medical Ethics, University of Chicago, Chicago, IL 60637, USA
J Clin Oncol 25:3488-94. 2007....
Determination of the optimal modulatory dose of O6-benzylguanine in patients with surgically resectable tumorsM Eileen Dolan
Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA
Clin Cancer Res 8:2519-23. 2002..e., 100 and 120 mg/m2). The objective of our study was to compare these doses by measuring AGT in surgically removed specimens after treatment with BG...
Uridine 5'-diphospho-glucuronosyltransferase genetic polymorphisms and response to cancer chemotherapyJacqueline Ramirez
Department of Medicine, The University of Chicago, 5841 S Maryland Avenue, MC2115, Chicago, IL 60637, USA
Future Oncol 6:563-85. 2010....
Analysis of the yield of phase II combination therapy trials in medical oncologyMichael L Maitland
Section of Hematology Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
Clin Cancer Res 16:5296-302. 2010..We hypothesized that recognized flaws of single-arm trials could be magnified in combination treatment studies, leading to many reported positive phase II trials but with a low fraction resulting in practice-changing phase III trials...
The Werner's syndrome 4330T>C (Cys1367Arg) gene variant does not affect the in vitro cytotoxicity of topoisomerase inhibitors and platinum compoundsFederico Innocenti
Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, MC 2115, Chicago, IL 60637, USA
Cancer Chemother Pharmacol 63:881-7. 2009..We studied whether the 4330T>C variant confers altered drug sensitivity in vitro...
A phase I and pharmacokinetic study of the quinoxaline antitumour Agent R(+)XK469 in patients with advanced solid tumoursSamir D Undevia
Department of Medicine, Section of Hematology Oncology, University of Chicago, Chicago, IL 60637, USA
Eur J Cancer 44:1684-92. 2008..Preclinical studies suggested that efficacy was independent of schedule but that toxicity was decreased by dividing the dose...
Ambulatory monitoring detects sorafenib-induced blood pressure elevations on the first day of treatmentMichael L Maitland
Section of Hematology Oncology, Department of Medicine, University of Chicago, Chicago, Illinois, USA
Clin Cancer Res 15:6250-7. 2009..This prospective, single-center, cohort study characterized ambulatory blood pressure monitoring as an early pharmacodynamic biomarker of VEGF signaling pathway inhibition by sorafenib...
Pharmacogenetic testing for uridine diphosphate glucuronosyltransferase 1A1 polymorphisms: are we there yet?Minoli A Perera
Sections of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, Illinois, USA
Pharmacotherapy 28:755-68. 2008..In addition, ethical and logistic implications of pharmacogenetic testing exist...
A phase I and pharmacokinetic study of XK469R (NSC 698215), a quinoxaline phenoxypropionic acid derivative, in patients with refractory acute leukemiaWendy Stock
Section of Hematology Oncology, University of Chicago Cancer Research Center, 5841 S Maryland, M C 2115, Chicago, IL 60637, USA
Invest New Drugs 26:331-8. 2008..No correlation was observed between the development of DLT and pharmacokinetics. The RTPD is 1,750 mg. XK469R induced hematological responses in patients with refractory leukemia at tolerable doses...
Genomic assessment of a multikinase inhibitor, sorafenib, in a rodent model of pulmonary hypertensionLiliana Moreno-Vinasco
Section of Pulmonary and Critical Care Medicine, Department of Medicine, Pritzker School of Medicine, University of Chicago, Chicago, Illinois 60637, USA
Physiol Genomics 33:278-91. 2008..In summary, sorafenib represents a novel potential treatment for severe PH with the MAPK cascade a potential canonical target...
Phase I study of the ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde-thiosemicarbazone (3-AP) in combination with high dose cytarabine in patients with advanced myeloid leukemiaOlatoyosi M Odenike
Section of Hematology Oncology, Department of Medicine, University of Chicago Medical Center, 5841 S Maryland Avenue, MC 2115, Chicago, IL 60637 1470, USA
Invest New Drugs 26:233-9. 2008..The primary objective of the study was to establish the maximum tolerated dose of 3-AP when given in combination with a fixed dose of cytarabine...
Single nucleotide polymorphism discovery and functional assessment of variation in the UDP-glucuronosyltransferase 2B7 geneFederico Innocenti
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
Pharmacogenet Genomics 18:683-97. 2008..The genetic basis of interindividual variability in UGT2B7 function is unknown. This study aimed to discover novel gene variants of functional significance...
Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokineticsFederico Innocenti
The University of Chicago, Chicago, IL 60637, USA
J Clin Oncol 27:2604-14. 2009..We aim to identify genetic variation, in addition to the UGT1A1*28 polymorphism, that can explain the variability in irinotecan (CPT-11) pharmacokinetics and neutropenia in cancer patients...
Modulation of irinotecan with cyclosporine: a phase II trial in advanced colorectal cancerApurva A Desai
Section of Hematology Oncology, University of Chicago, 5841 S Maryland Avenue, MC 2115, Chicago, IL 60637, USA
Cancer Chemother Pharmacol 56:421-6. 2005..Hence, we conducted this phase II trial in patients with colorectal cancer (CRC) to further evaluate the toxicity and activity of irinotecan modulated with cyclosporine...
A phase I trial of escalating doses of trastuzumab combined with daily subcutaneous interleukin 2: report of cancer and leukemia group B 9661Gini F Fleming
Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA
Clin Cancer Res 8:3718-27. 2002..The purpose of this study was to determine the toxicity of escalating doses of trastuzumab when combined with a fixed dose regimen of interleukin (IL)-2...
Dose-ranging study of the safety and pharmacokinetics of atrasentan in patients with refractory malignanciesChristopher W Ryan
Section of Hematology Oncology, Department of Medicine, Cancer Research Center, and Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, and Abbott Laboratories, Abbott Park, Illinois, USA
Clin Cancer Res 10:4406-11. 2004..This Phase I study sought to determine the toxicity and pharmacokinetics of daily atrasentan in a population of both female and male subjects with advanced malignancies...
A phase I trial of gemcitabine plus cladribine in patients with advanced hematologic malignant diseasesOlatoyosi M Odenike
Section of Hematology Oncology, Department of Medicine, University of Chicago, 5841 S Maryland Avenue, MC 2115, Chicago, IL 60637 1470, USA
Cancer Chemother Pharmacol 54:553-61. 2004....
Irinotecan treatment in cancer patients with UGT1A1 polymorphismsFederico Innocenti
Department of Medicine, Committee on Clinical Pharmacology and Pharmacogenomics, Cancer Research Center, University of Chicago, Chicago, Illinois, USA
Oncology (Williston Park) 17:52-5. 2003..The results of these association studies showed that preliminary genotyping of the (TA)n polymorphism might predict the occurrence of toxicity in genetically predisposed patients...
A phase I study of suramin with once- or twice-monthly dosing in patients with advanced cancerChristopher W Ryan
Department of Medicine, Section of Hematology Oncology, University of Chicago MC2115, 5841S Maryland Ave, Chicago, IL 60637, USA
Cancer Chemother Pharmacol 50:1-5. 2002..The purpose of this study was to determine the maximum tolerated dose and toxicities of suramin when administered using a fixed dosing scheme on a once- or twice-monthly schedule...
Dose-escalating study of capecitabine plus gemcitabine combination therapy in patients with advanced cancerRichard L Schilsky
Department of Medicine, Section of Hematology Oncology, Cancer Research Center and Committee on Clinical Pharmacology, University of Chicago, Chicago, IL 60637, USA
J Clin Oncol 20:582-7. 2002..The goals of this phase I study were to determine the maximum-tolerated doses of capecitabine and gemcitabine in patients with advanced cancer and to describe the dose-limiting toxicities (DLT) and safety profile of this combination...
Delivery of a liposomal c-raf-1 antisense oligonucleotide by weekly bolus dosing in patients with advanced solid tumors: a phase I studyCharles M Rudin
The University of Chicago, Chicago, Illinois, USA
Clin Cancer Res 10:7244-51. 2004..Liposomal formulation may promote better intratumoral AON delivery and inhibit degradation in vivo. We conducted the first clinical evaluation of this concept using a liposomal AON complementary to the c-raf-1 proto-oncogene (LErafAON)...
Dose-ranging pharmacodynamic study of tipifarnib (R115777) in patients with relapsed and refractory hematologic malignanciesTodd M Zimmerman
Department of Medicine, Section of Hematology Oncology, University of Chicago, Chicago, IL, USA
J Clin Oncol 22:4816-22. 2004..Tipifarnib, an orally bioavailable inhibitor of farnesyl transferase, has activity in hematologic malignancies, but the dose required to achieve the proposed biologic end point, inhibition of farnesylation, is unknown...
Heritability and linkage analysis of sensitivity to cisplatin-induced cytotoxicityM Eileen Dolan
Department of Medicine, and Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Illinois 60637, USA
Cancer Res 64:4353-6. 2004..These data show the power of using large pedigrees that have been extensively genotyped for evaluating the genetic contribution to sensitivity to cell growth inhibition by anticancer agents...
Successful implementation of the randomized discontinuation trial design: an application to the study of the putative antiangiogenic agent carboxyaminoimidazole in renal cell carcinoma--CALGB 69901Walter M Stadler
University of Chicago, Section of Hematology Oncology, 5841 S Maryland Ave, MC 2115, Chicago, IL 60637, USA
J Clin Oncol 23:3726-32. 2005..To assess the disease-stabilizing activity of carboxyaminoimidazole (CAI) in patients with metastatic renal cell cancer (RCC) using a randomized discontinuation trial (RDT) design...
Estimation of the effect of food on the disposition of oral 5-fluorouracil in combination with eniluracilDale R Shepard
University of Chicago, 5841 S. Maryland Ave, Chicago, IL 60637, USA
Cancer Chemother Pharmacol 49:398-402. 2002..Further investigation of the incorporation of population pharmacokinetic approaches in food effect studies is warranted...
EGFR pharmacogenomics: the story continues to mutate and evolveApurva A Desai
Section of Hematology and Oncology, University of Chicago, Illinois 60637, USA
Am J Pharmacogenomics 5:137-9. 2005
The 1200 patients project: creating a new medical model system for clinical implementation of pharmacogenomicsP H O'Donnell
Department of Medicine, The University of Chicago, Chicago, Illinois, USA
Clin Pharmacol Ther 92:446-9. 2012..We describe our institutional pharmacogenomics-implementation project, "The 1200 Patients Project," a model designed to overcome these barriers and facilitate the availability of pharmacogenomic information for personalized prescribing...
Models of excellence: improving oncology drug developmentM R Sharma
1 Department of Medicine, University of Chicago, Chicago, Illinois, USA 2 Comprehensive Cancer Center, University of Chicago, Chicago, Illinois, USA 3 Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, Illinois, USA
Clin Pharmacol Ther 92:548-50. 2012....
Phase I study of pegylated liposomal doxorubicin, paclitaxel, and cisplatin in patients with advanced solid tumorsC Eng
Department of Medicine, Section of Hematology Oncology, University of Chicago, IL, USA
Ann Oncol 12:1743-7. 2001..The mean decline in left ventricular ejection fraction (LVEF) after 2 cycles was 5 percentage points (P = 0.012). CONCLUSION: The combination of pegylated liposomal doxorubicin, paclitaxel and cisplatin is feasible without G-CSF support...
Phase I and pharmacokinetic study of 24-hour infusion 5-fluorouracil and leucovorin in patients with organ dysfunctionG F Fleming
Department of Medicine, University of Chicago Medical Center, IL 60637 1470, USA
Ann Oncol 14:1142-7. 2003..Patients with hepatic or renal dysfunction are often treated with 5-fluorouracil (5-FU), but there are few data to confirm the safety of this practice...
Relationship of EGFR mutations, expression, amplification, and polymorphisms to epidermal growth factor receptor inhibitors in the NCI60 cell linesWanqing Liu
Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA
Clin Cancer Res 13:6788-95. 2007..We aimed to determine if there are interactions between EGFR expression, mutations, polymorphisms, and gene amplification, and whether these factors are associated with variability in response to EGFR inhibitors...
"Irinogenetics" and UGT1A: from genotypes to haplotypesFederico Innocenti
Department of Medicine, Committee on Clinical Pharmacology and Pharmacogenomics, Cancer Research Center, University of Chicago, IL 60637, USA
Clin Pharmacol Ther 75:495-500. 2004
A phase I study of cantuzumab mertansine administered as a single intravenous infusion once weekly in patients with advanced solid tumorsPaul R Helft
University of Chicago, Chicago, Illinois, USA
Clin Cancer Res 10:4363-8. 2004..The evidence of antitumor activity suggests that additional clinical development is warranted, with a focus on tumors that express high levels of CanAg and which are known to be sensitive to antimicrotubule agents...
Measuring response in a post-RECIST world: from black and white to shades of greyLaura C Michaelis
Section of Hematology Oncology, University of Chicago, 5841 S Maryland Avenue, MC 2115, Chicago, Illinois 60637, USA
Nat Rev Cancer 6:409-14. 2006..We will argue that the current drug development environment dictates different outcome measurements and therefore more imaginative and rigorous early-phase trial designs...
Phase I clinical trial of CEP-2563 dihydrochloride, a receptor tyrosine kinase inhibitor, in patients with refractory solid tumorsSamir D Undevia
Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA
Invest New Drugs 22:449-58. 2004..The recommended phase II dose is 256 mg/m(2)/d. Rapid dose escalation with single patient cohorts was a safe and efficient method of conducting this phase I trial...
In vitro characterization of hepatic flavopiridol metabolism using human liver microsomes and recombinant UGT enzymesJacqueline Ramirez
Department of Medicine, University of Chicago, Illinois 60637, USA
Pharm Res 19:588-94. 2002....
The value meal: how to save $1,700 per month or more on lapatinibMark J Ratain
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA
J Clin Oncol 25:3397-8. 2007
Update on pharmacogenetics in cancer chemotherapyF Innocenti
Department of Medicine, Committee on Clinical Pharmacology and Pharmacogenomics, Cancer Research Center, The University of Chicago, Chicago, IL, USA
Eur J Cancer 38:639-44. 2002....
Prediction of CYP3A4 enzyme activity using haplotype tag SNPs in African AmericansM A Perera
Committee on Clinical Pharmacology and Pharmacogenomics, Division of Biological Sciences, University of Chicago, Chicago, IL, USA
Pharmacogenomics J 9:49-60. 2009..This study marks the first systematic evaluation of coding and noncoding variation that may contribute to CYP3A phenotypic variability...
Rapid response to 2'-deoxycoformycin in advanced hairy cell leukemia after failure of interferons alpha and gammaB C Lembersky
Department of Medicine, University of Chicago Pritzker School of Medicine, IL
Am J Hematol 27:60-2. 1988..Subsequent treatment with 2'-deoxycoformycin (dCF) administered biweekly for 12 wk resulted in a complete hematological remission which has continued for 16 months without additional therapy...
Chronic daily low dose of 4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione (Oltipraz) in patients with previously resected colon polyps and first degree female relatives of breast cancer patientsA B Benson
Department of Medicine, Northwestern University Medical School, and Robert H Lurie Comprehensive Cancer Center Chicago, Illinois 60611, USA
Clin Cancer Res 6:3870-7. 2000..Further investigation of dose/schedule and biological end points is ongoing...
Rapamycin: something old, something new, sometimes borrowed and now renewedC M Hartford
Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, Illinois, USA
Clin Pharmacol Ther 82:381-8. 2007..Given the multitude of potential applications for this class of agents and the decrease in cost that can be expected upon the expiration of sirolimus patents, renewed focus on this agent is warranted...
Randomized phase II trials: a long-term investment with promising returnsManish R Sharma
Department of Medicine, University of Chicago, Chicago, IL 60637 1470, USA
J Natl Cancer Inst 103:1093-100. 2011..We conclude that randomized phase II trials are a worthy investment considering finite patient and financial resources and should be the rule rather than the exception for evaluating novel therapies in oncology...
Pharmacogenomic and pharmacokinetic determinants of erlotinib toxicityCharles M Rudin
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, David H Koch Cancer Research Building, Room 544, 1550 Orleans St, Baltimore, MD 21231, USA
J Clin Oncol 26:1119-27. 2008..To assess the pharmacogenomic and pharmacokinetic determinants of skin rash and diarrhea, the two primary dose-limiting toxicities of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib...
Research Grants
- CANCER AND LEUKEMIA GROUP B--PET COMMITTEEMark Ratain; Fiscal Year: 2002..Since many of the studies include analysis of pharmacological specimens, the Committee utilizes three core laboratories--at the University of Chicago, the University of Maryland and the University of Tennessee. ..
- Phase I Clinical Trials of Anti-Cancer AgentsMark Ratain; Fiscal Year: 2007..This application also includes a proposal for the creation of an Early Clinical Trials Network to facilitate inter-institutional collaborations involving NCI-sponsored early clinical trials. ..
- CLINICAL THERAPEUTICSMark Ratain; Fiscal Year: 2007..abstract_text> ..
- PHARMACOGENETICS OF ANTICANCER AGENTS RESEARCH GROUPMark Ratain; Fiscal Year: 2007....
