M J Ratain

Summary

Affiliation: University of Chicago
Country: USA

Publications

  1. pmc Models of excellence: improving oncology drug development
    M R Sharma
    Department of Medicine, University of Chicago, Illinois, USA
    Clin Pharmacol Ther 92:548-50. 2012
  2. pmc Searching for tissue-specific expression pattern-linked nucleotides of UGT1A isoforms
    Wei Zhang
    Section of Hematology Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, United States of America
    PLoS ONE 2:e396. 2007
  3. pmc Evaluating the activity of temsirolimus in neuroendocrine cancer
    P H O'Donnell
    Br J Cancer 96:177; author reply 178-9. 2007
  4. pmc Genome-wide identification of genetic determinants for the cytotoxicity of perifosine
    Wei Zhang
    Section of Hematology Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
    Hum Genomics 3:53-70. 2008
  5. pmc Exploring the relationship between polymorphic (TG/CA)n repeats in intron 1 regions and gene expression
    Wei Zhang
    Section of Hematology Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
    Hum Genomics 3:236-45. 2009
  6. pmc Unsupported off-label chemotherapy in metastatic colon cancer
    Jonas A de Souza
    Section of Hematology Oncology, The University of Chicago Medicine, Chicago, IL, USA
    BMC Health Serv Res 12:481. 2012
  7. pmc A genome-wide integrative study of microRNAs in human liver
    Eric R Gamazon
    Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
    BMC Genomics 14:395. 2013
  8. pmc 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
  9. ncbi request reprint From bedside to bench to bedside to clinical practice: an odyssey with irinotecan
    Mark 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
  10. doi request reprint Individualizing dosing of irinotecan
    Mark 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

Research Grants

  1. CANCER AND LEUKEMIA GROUP B--PET COMMITTEE
    Mark Ratain; Fiscal Year: 2002
  2. Phase I Clinical Trials of Anti-Cancer Agents
    Mark Ratain; Fiscal Year: 2007
  3. CLINICAL THERAPEUTICS
    Mark Ratain; Fiscal Year: 2007
  4. PHARMACOGENETICS OF ANTICANCER AGENTS RESEARCH GROUP
    Mark Ratain; Fiscal Year: 2007

Collaborators

Detail Information

Publications125 found, 100 shown here

  1. pmc Models of excellence: improving oncology drug development
    M R Sharma
    Department of Medicine, University of Chicago, Illinois, USA
    Clin Pharmacol Ther 92:548-50. 2012
    ....
  2. pmc Searching for tissue-specific expression pattern-linked nucleotides of UGT1A isoforms
    Wei Zhang
    Section of Hematology Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, United States of America
    PLoS ONE 2:e396. 2007
    ....
  3. pmc Evaluating the activity of temsirolimus in neuroendocrine cancer
    P H O'Donnell
    Br J Cancer 96:177; author reply 178-9. 2007
  4. pmc Genome-wide identification of genetic determinants for the cytotoxicity of perifosine
    Wei Zhang
    Section of Hematology Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
    Hum Genomics 3:53-70. 2008
    ..These genes could be targets for further studies using candidate-gene approaches. The results also provided insights into the pharmacodynamics of perifosine...
  5. pmc Exploring the relationship between polymorphic (TG/CA)n repeats in intron 1 regions and gene expression
    Wei Zhang
    Section of Hematology Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
    Hum Genomics 3:236-45. 2009
    ..A more comprehensive evaluation of the relationship between these repeats and gene expression, potentially in other tissues, may be necessary to illustrate their roles in gene regulation in the future...
  6. pmc Unsupported off-label chemotherapy in metastatic colon cancer
    Jonas A de Souza
    Section of Hematology Oncology, The University of Chicago Medicine, Chicago, IL, USA
    BMC Health Serv Res 12:481. 2012
    ..Newer systemic therapies have the potential to decrease morbidity and mortality from metastatic colorectal cancer, yet such therapies are costly and have side effects. Little is known about their non-evidence-based use...
  7. pmc A genome-wide integrative study of microRNAs in human liver
    Eric R Gamazon
    Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
    BMC Genomics 14:395. 2013
    ..The study of microRNAs in human liver tissue promises to clarify the therapeutic and diagnostic value of this important regulatory mechanism of gene expression...
  8. pmc 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
  9. ncbi request reprint From bedside to bench to bedside to clinical practice: an odyssey with irinotecan
    Mark 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
  10. doi request reprint Individualizing dosing of irinotecan
    Mark 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...
  11. doi request reprint Merrill Jon Egorin, MD, 1948-2010
    M 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...
  12. ncbi request reprint Personalized medicine: building the GPS to take us there
    M 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
  13. doi request reprint Optimising the design of phase II oncology trials: the importance of randomisation
    Mark 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
    ....
  14. ncbi request reprint The cancer and leukemia group B pharmacology and experimental therapeutics committee: a historical perspective
    Mark 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...
  15. ncbi request reprint Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma
    Mark 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...
  16. ncbi request reprint 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 malignancies
    S 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...
  17. ncbi request reprint Phase I study of ZD9331 on short daily intravenous bolus infusion for 5 days every 3 weeks with fixed dosing recommendations
    B 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...
  18. ncbi request reprint Phenotype-genotype correlation of in vitro SN-38 (active metabolite of irinotecan) and bilirubin glucuronidation in human liver tissue with UGT1A1 promoter polymorphism
    L 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...
  19. ncbi request reprint A phase I study of sirolimus and bevacizumab in patients with advanced malignancies
    E 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...
  20. ncbi request reprint A phase I study of the oral combination of CI-994, a putative histone deacetylase inhibitor, and capecitabine
    S D Undevia
    Section of Hematology Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA
    Ann Oncol 15:1705-11. 2004
    ..This study was conducted to determine the toxicity profile, maximum tolerated dose (MTD) and pharmacokinetics of the putative histone deacetylase inhibitor CI-994 in combination with capecitabine...
  21. ncbi request reprint Phase I clinical and pharmacogenetic study of weekly TAS-103 in patients with advanced cancer
    R 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...
  22. pmc Estimation of renal cell carcinoma treatment effects from disease progression modeling
    M 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...
  23. ncbi request reprint Phase I clinical and pharmacologic study of eniluracil plus fluorouracil in patients with advanced cancer
    R 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
    ....
  24. pmc A dosing/cross-development study of the multikinase inhibitor sorafenib in patients with pulmonary arterial hypertension
    M 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...
  25. ncbi request reprint O6-benzylguanine in humans: metabolic, pharmacokinetic, and pharmacodynamic findings
    M 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)...
  26. ncbi request reprint Phase I clinical and pharmacological study of O6-benzylguanine followed by carmustine in patients with advanced cancer
    R 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...
  27. ncbi request reprint Lack of association between common polymorphisms in UGT1A9 and gene expression and activity
    Jacqueline 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...
  28. pmc The UGT1A1*28 polymorphism correlates with erlotinib's effect on SN-38 glucuronidation
    Yong 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...
  29. ncbi request reprint Body surface area as a determinant of pharmacokinetics and drug dosing
    M 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...
  30. ncbi request reprint Phase I Trial of ISIS 5132, an antisense oligonucleotide inhibitor of c-raf-1, administered by 24-hour weekly infusion to patients with advanced cancer
    C M Rudin
    Section of Hematology Oncology, University of Chicago Medical Center, Chicago, Illinois 60637 1470, USA
    Clin Cancer Res 7:1214-20. 2001
    ....
  31. ncbi request reprint 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 cancer
    Theodore 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...
  32. ncbi request reprint UGT1A1*28 genotype affects the in-vitro glucuronidation of thyroxine in human livers
    Andrea 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...
  33. ncbi request reprint A phase I trial of pharmacologic modulation of irinotecan with cyclosporine and phenobarbital
    Federico 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...
  34. ncbi request reprint A comparison of the pharmacokinetics and pharmacodynamics of docetaxel between African-American and Caucasian cancer patients: CALGB 9871
    Lionel 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...
  35. pmc Pharmacogenetics and pharmacogenomics of anticancer agents
    R 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
    ....
  36. ncbi request reprint UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity
    L 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...
  37. ncbi request reprint Inflammation of actinic keratoses subsequent to therapy with sorafenib, a multitargeted tyrosine-kinase inhibitor
    M 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...
  38. ncbi request reprint Hepatocyte nuclear factor-1 alpha is associated with UGT1A1, UGT1A9 and UGT2B7 mRNA expression in human liver
    J 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...
  39. ncbi request reprint Study of cohort-specific consent and patient control in phase I cancer trials
    C 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
    ....
  40. ncbi request reprint Pharmacogenetics of anticancer agents: lessons from amonafide and irinotecan
    F 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...
  41. ncbi request reprint Phase I study of an oral formulation of ZD9331 administered daily for 28 days
    Michael 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
    ..To define the maximum-tolerated dose and dose-limiting toxicities (DLTs) of an oral formulation of ZD9331, a novel thymidylate synthase inhibitor that is not a substrate for folylpolyglutamate synthase...
  42. ncbi request reprint Pharmacokinetic modulation of oral etoposide by ketoconazole in patients with advanced cancer
    Wei 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...
  43. ncbi request reprint Haplotype structure of the UDP-glucuronosyltransferase 1A1 promoter in different ethnic groups
    Federico 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...
  44. ncbi request reprint Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan
    Federico 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...
  45. pmc Dynamic contrast-enhanced magnetic resonance imaging pharmacodynamic biomarker study of sorafenib in metastatic renal carcinoma
    Olwen 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...
  46. ncbi request reprint 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...
  47. ncbi request reprint Phase 1 dose escalation study of docetaxel with filgrastim support in patients with advanced solid tumors
    Gregory 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...
  48. ncbi request reprint Phase I and pharmacokinetic study of 24-hour infusion 5-fluorouracil and leucovorin in patients with organ dysfunction
    G 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...
  49. ncbi request reprint Phase II trial of paclitaxel and topotecan with granulocyte colony-stimulating factor support in stage IV breast cancer
    G 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...
  50. ncbi request reprint Pharmacogenetics in cancer treatment
    R 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...
  51. ncbi request reprint A phase I study of antisense oligonucleotide GTI-2040 given by continuous intravenous infusion in patients with advanced solid tumors
    A A Desai
    Section of Hematology and Oncology, University of Chicago, Chicago, IL 60637, USA
    Ann Oncol 16:958-65. 2005
    ..Plasma pharmacokinetics of GTI-2040 and suppression of RNR expression in peripheral blood mononuclear cells were also studied...
  52. ncbi request reprint A pharmacogenetic study of uridine diphosphate-glucuronosyltransferase 2B7 in patients receiving morphine
    Michael 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...
  53. ncbi request reprint Study of the genetic determinants of UGT1A1 inducibility by phenobarbital in cultured human hepatocytes
    Jacqueline 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...
  54. ncbi request reprint 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 cancer
    Sridhar 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...
  55. ncbi request reprint Haplotypes of variants in the UDP-glucuronosyltransferase1A9 and 1A1 genes
    Federico 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...
  56. pmc The role of pharmacogenetics in cancer therapeutics
    Wei 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
    ....
  57. pmc Prediction of CYP3A4 enzyme activity using haplotype tag SNPs in African Americans
    M 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...
  58. doi request reprint The 1200 patients project: creating a new medical model system for clinical implementation of pharmacogenomics
    P 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...
  59. ncbi request reprint Epirubicin glucuronidation is catalyzed by human UDP-glucuronosyltransferase 2B7
    F 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...
  60. ncbi request reprint 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 neck
    B 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...
  61. ncbi request reprint Phase II and pharmacodynamic studies of pyrazine diazohydroxide (NSC 361456) in patients with advanced renal and colorectal cancer
    N 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...
  62. doi request reprint Nonprofit biomedical companies
    R 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...
  63. pmc A phase I and pharmacokinetic study of the quinoxaline antitumour Agent R(+)XK469 in patients with advanced solid tumours
    Samir 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...
  64. pmc Analysis of the yield of phase II combination therapy trials in medical oncology
    Michael 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...
  65. pmc The Werner's syndrome 4330T>C (Cys1367Arg) gene variant does not affect the in vitro cytotoxicity of topoisomerase inhibitors and platinum compounds
    Federico 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...
  66. pmc Single nucleotide polymorphism discovery and functional assessment of variation in the UDP-glucuronosyltransferase 2B7 gene
    Federico 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...
  67. pmc R(+)XK469 inhibits hydroxylation of S-warfarin by CYP2C9
    Wei 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...
  68. ncbi request reprint A phase I and pharmacokinetic study of XK469R (NSC 698215), a quinoxaline phenoxypropionic acid derivative, in patients with refractory acute leukemia
    Wendy 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...
  69. ncbi request reprint Attitudes toward research participation and investigator conflicts of interest among advanced cancer patients participating in early phase clinical trials
    Stacy 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
    ....
  70. pmc Genomic assessment of a multikinase inhibitor, sorafenib, in a rodent model of pulmonary hypertension
    Liliana 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...
  71. pmc Ambulatory monitoring detects sorafenib-induced blood pressure elevations on the first day of treatment
    Michael 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...
  72. pmc Uridine 5'-diphospho-glucuronosyltransferase genetic polymorphisms and response to cancer chemotherapy
    Jacqueline Ramirez
    Department of Medicine, The University of Chicago, 5841 S Maryland Avenue, MC2115, Chicago, IL 60637, USA
    Future Oncol 6:563-85. 2010
    ....
  73. pmc Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics
    Federico 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...
  74. ncbi request reprint 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 leukemia
    Olatoyosi 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...
  75. ncbi request reprint EGFR pharmacogenomics: the story continues to mutate and evolve
    Apurva A Desai
    Section of Hematology and Oncology, University of Chicago, Illinois 60637, USA
    Am J Pharmacogenomics 5:137-9. 2005
  76. ncbi request reprint Delivery of a liposomal c-raf-1 antisense oligonucleotide by weekly bolus dosing in patients with advanced solid tumors: a phase I study
    Charles 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)...
  77. ncbi request reprint A phase I trial of gemcitabine plus cladribine in patients with advanced hematologic malignant diseases
    Olatoyosi 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
    ....
  78. ncbi request reprint A Phase II trial of suramin monthly x 3 for hormone-refractory prostate carcinoma
    Nicholas J Vogelzang
    Section of Hematology Oncology, Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA
    Cancer 100:65-71. 2004
    ....
  79. ncbi request reprint Dose-ranging study of the safety and pharmacokinetics of atrasentan in patients with refractory malignancies
    Christopher 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...
  80. ncbi request reprint Heritability and linkage analysis of sensitivity to cisplatin-induced cytotoxicity
    M 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...
  81. ncbi request reprint Estimation of the effect of food on the disposition of oral 5-fluorouracil in combination with eniluracil
    Dale R Shepard
    University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637, USA
    Cancer Chemother Pharmacol 49:398-402. 2002
    ..To determine the effect of food on the pharmacokinetics of 5-fluoruracil (5-FU) taken orally with eniluracil and to compare the performance of different pharmacokinetic analysis methods in the detection a potential food-drug interaction...
  82. ncbi request reprint Dose-escalating study of capecitabine plus gemcitabine combination therapy in patients with advanced cancer
    Richard 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...
  83. ncbi request reprint Irinotecan treatment in cancer patients with UGT1A1 polymorphisms
    Federico 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...
  84. ncbi request reprint A phase I study of suramin with once- or twice-monthly dosing in patients with advanced cancer
    Christopher 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...
  85. ncbi request reprint A phase I trial of escalating doses of trastuzumab combined with daily subcutaneous interleukin 2: report of cancer and leukemia group B 9661
    Gini 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...
  86. ncbi request reprint Dose-ranging pharmacodynamic study of tipifarnib (R115777) in patients with relapsed and refractory hematologic malignancies
    Todd 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...
  87. doi request reprint 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...
  88. ncbi request reprint Modulation of irinotecan with cyclosporine: a phase II trial in advanced colorectal cancer
    Apurva 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...
  89. ncbi request reprint Pharmacogenetics of irinotecan: clinical perspectives on the utility of genotyping
    Federico Innocenti
    The University of Chicago, Committee on Clinical Pharmacology and Pharmacogenomics, Chicago, IL, USA
    Pharmacogenomics 7:1211-21. 2006
    ....
  90. ncbi request reprint 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
    ....
  91. ncbi request reprint Determination of the optimal modulatory dose of O6-benzylguanine in patients with surgically resectable tumors
    M 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...
  92. ncbi request reprint Successful implementation of the randomized discontinuation trial design: an application to the study of the putative antiangiogenic agent carboxyaminoimidazole in renal cell carcinoma--CALGB 69901
    Walter 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...
  93. ncbi request reprint Update on pharmacogenetics in cancer chemotherapy
    F 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
    ....
  94. ncbi request reprint Challenges in interpreting the evidence for genetic predictors of ototoxicity
    M J Ratain
    Department of Medicine, Comprehensive Cancer Center and Center for Personalized Therapeutics, The University of Chicago, Chicago, Illinois, USA
    Clin Pharmacol Ther 94:631-5. 2013
    ..We summarize statistical issues not fully addressed by the authors that appear to have confounded the results of their studies. ..
  95. ncbi request reprint Phase I study of pegylated liposomal doxorubicin, paclitaxel, and cisplatin in patients with advanced solid tumors
    C 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...
  96. ncbi request reprint Phase I clinical trial of CEP-2563 dihydrochloride, a receptor tyrosine kinase inhibitor, in patients with refractory solid tumors
    Samir 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...
  97. ncbi request reprint Relationship of EGFR mutations, expression, amplification, and polymorphisms to epidermal growth factor receptor inhibitors in the NCI60 cell lines
    Wanqing 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...
  98. ncbi request reprint "Irinogenetics" and UGT1A: from genotypes to haplotypes
    Federico 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
  99. ncbi request reprint In vitro characterization of hepatic flavopiridol metabolism using human liver microsomes and recombinant UGT enzymes
    Jacqueline Ramirez
    Department of Medicine, University of Chicago, Illinois 60637, USA
    Pharm Res 19:588-94. 2002
    ....
  100. ncbi request reprint Measuring response in a post-RECIST world: from black and white to shades of grey
    Laura 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...

Research Grants6

  1. CANCER AND LEUKEMIA GROUP B--PET COMMITTEE
    Mark 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. ..
  2. Phase I Clinical Trials of Anti-Cancer Agents
    Mark 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. ..
  3. CLINICAL THERAPEUTICS
    Mark Ratain; Fiscal Year: 2007
    ..abstract_text> ..
  4. PHARMACOGENETICS OF ANTICANCER AGENTS RESEARCH GROUP
    Mark Ratain; Fiscal Year: 2007
    ....