title: Potential cytochrome P-450 drug-drug interactions in adults with metastatic solid tumors and effect on eligibility for Phase I clinical trials.
abstract: OBJECTIVE
  Potential cytochrome P-450 (CYP) drug-drug interactions in adults with metastatic solid tumors and their effect on eligibility for Phase I clinical trials were characterized.
  
  
  METHODS
  This study included adult patients with metastatic solid tumors seen by a medical oncologist from January 2008 through July 2011. The medications used by these patients were identified. Each medication's potential for interacting with CYP isozymes was also characterized. Medication changes required to meet Phase I trial eligibility criteria were also reviewed.
  
  
  RESULTS
  Data from 1773 patients were analyzed: 1489 were not enrolled in a Phase I trial and 284 were enrolled in a Phase I trial. Polypharmacy was significantly more prevalent in the group enrolled in a Phase I trial compared with those not enrolled (95% versus 80%, p < 0.001). The majority of patients not enrolled in a Phase I trial were taking at least one CYP isozyme inhibitor (87%) and at least one CYP isozyme inducer (45%). In a separate analysis, four Phase I trials were evaluated. Of 295 screened patients, 3.2% could not enroll due to concurrent medications. Charts from 74 enrolled patients revealed 655 concurrent medications—93 medications required further review for eligibility involving 51 (69%) of patients. Of the 93 medications, 38 (41%) were stopped and 41 (44%) were changed for the study.
  
  
  CONCLUSIONS
  Polypharmacy and the use of medications that interact with CYP isoyzmes were common in adult patients with metastatic solid tumors. Patients enrolling in Phase I studies often require medication changes to meet eligibility requirements.
authors.affiliation: Kari B. Wisinski, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, University of Wisconsin (UW), Madison, and Assistant Professor, UW Carbone Cancer Center, Madison. Colby A. Cantu, B.S., is Medical Student, School of Medicine and Public Health, UW. Jens Eickhoff, Ph.D., is Senior Scientist, Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, UW. Kurt Osterby, B.S., is Senior Decision Support Analyst, UW Hospital and Clinics, Madison. Amye J. Tevaarwerk, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, UW, and Assistant Professor, UW Carbone Cancer Center. Jennifer Heideman, R.N., is Program Manager, School of Medicine and Public Health, UW, and Program Manager, UW Carbone Cancer Center. Glenn Liu, M.D., is Associate Professor of Medicine, School of Medicine and Public Health, UW, and UW Carbone Cancer Center. George Wilding, M.D., is Professor of Medicine, School of Medicine and Public Health, UW, and Professor, UW Carbone Cancer Center. Susan Johnston, Pharm.D., is Pharmaceutical Research Center Manager, UW Carbone Cancer Center, and UW Hospital and Clinics. Jill M. Kolesar, Pharm.d., is Professor of Pharmacy, School of Pharmacy, UW, and Faculty Supervisor, Analytical Laboratory for Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics, UW Carbone Cancer Center. kbwisinski@medicine.wisc.edu.
authors.forename: Kari B
authors.initials: KB
authors.lastname: Wisinski
authors.affiliation: Kari B. Wisinski, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, University of Wisconsin (UW), Madison, and Assistant Professor, UW Carbone Cancer Center, Madison. Colby A. Cantu, B.S., is Medical Student, School of Medicine and Public Health, UW. Jens Eickhoff, Ph.D., is Senior Scientist, Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, UW. Kurt Osterby, B.S., is Senior Decision Support Analyst, UW Hospital and Clinics, Madison. Amye J. Tevaarwerk, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, UW, and Assistant Professor, UW Carbone Cancer Center. Jennifer Heideman, R.N., is Program Manager, School of Medicine and Public Health, UW, and Program Manager, UW Carbone Cancer Center. Glenn Liu, M.D., is Associate Professor of Medicine, School of Medicine and Public Health, UW, and UW Carbone Cancer Center. George Wilding, M.D., is Professor of Medicine, School of Medicine and Public Health, UW, and Professor, UW Carbone Cancer Center. Susan Johnston, Pharm.D., is Pharmaceutical Research Center Manager, UW Carbone Cancer Center, and UW Hospital and Clinics. Jill M. Kolesar, Pharm.d., is Professor of Pharmacy, School of Pharmacy, UW, and Faculty Supervisor, Analytical Laboratory for Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics, UW Carbone Cancer Center.
authors.forename: Colby A
authors.initials: CA
authors.lastname: Cantu
authors.affiliation: Kari B. Wisinski, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, University of Wisconsin (UW), Madison, and Assistant Professor, UW Carbone Cancer Center, Madison. Colby A. Cantu, B.S., is Medical Student, School of Medicine and Public Health, UW. Jens Eickhoff, Ph.D., is Senior Scientist, Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, UW. Kurt Osterby, B.S., is Senior Decision Support Analyst, UW Hospital and Clinics, Madison. Amye J. Tevaarwerk, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, UW, and Assistant Professor, UW Carbone Cancer Center. Jennifer Heideman, R.N., is Program Manager, School of Medicine and Public Health, UW, and Program Manager, UW Carbone Cancer Center. Glenn Liu, M.D., is Associate Professor of Medicine, School of Medicine and Public Health, UW, and UW Carbone Cancer Center. George Wilding, M.D., is Professor of Medicine, School of Medicine and Public Health, UW, and Professor, UW Carbone Cancer Center. Susan Johnston, Pharm.D., is Pharmaceutical Research Center Manager, UW Carbone Cancer Center, and UW Hospital and Clinics. Jill M. Kolesar, Pharm.d., is Professor of Pharmacy, School of Pharmacy, UW, and Faculty Supervisor, Analytical Laboratory for Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics, UW Carbone Cancer Center.
authors.forename: Jens
authors.initials: J
authors.lastname: Eickhoff
authors.affiliation: Kari B. Wisinski, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, University of Wisconsin (UW), Madison, and Assistant Professor, UW Carbone Cancer Center, Madison. Colby A. Cantu, B.S., is Medical Student, School of Medicine and Public Health, UW. Jens Eickhoff, Ph.D., is Senior Scientist, Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, UW. Kurt Osterby, B.S., is Senior Decision Support Analyst, UW Hospital and Clinics, Madison. Amye J. Tevaarwerk, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, UW, and Assistant Professor, UW Carbone Cancer Center. Jennifer Heideman, R.N., is Program Manager, School of Medicine and Public Health, UW, and Program Manager, UW Carbone Cancer Center. Glenn Liu, M.D., is Associate Professor of Medicine, School of Medicine and Public Health, UW, and UW Carbone Cancer Center. George Wilding, M.D., is Professor of Medicine, School of Medicine and Public Health, UW, and Professor, UW Carbone Cancer Center. Susan Johnston, Pharm.D., is Pharmaceutical Research Center Manager, UW Carbone Cancer Center, and UW Hospital and Clinics. Jill M. Kolesar, Pharm.d., is Professor of Pharmacy, School of Pharmacy, UW, and Faculty Supervisor, Analytical Laboratory for Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics, UW Carbone Cancer Center.
authors.forename: Kurt
authors.initials: K
authors.lastname: Osterby
authors.affiliation: Kari B. Wisinski, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, University of Wisconsin (UW), Madison, and Assistant Professor, UW Carbone Cancer Center, Madison. Colby A. Cantu, B.S., is Medical Student, School of Medicine and Public Health, UW. Jens Eickhoff, Ph.D., is Senior Scientist, Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, UW. Kurt Osterby, B.S., is Senior Decision Support Analyst, UW Hospital and Clinics, Madison. Amye J. Tevaarwerk, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, UW, and Assistant Professor, UW Carbone Cancer Center. Jennifer Heideman, R.N., is Program Manager, School of Medicine and Public Health, UW, and Program Manager, UW Carbone Cancer Center. Glenn Liu, M.D., is Associate Professor of Medicine, School of Medicine and Public Health, UW, and UW Carbone Cancer Center. George Wilding, M.D., is Professor of Medicine, School of Medicine and Public Health, UW, and Professor, UW Carbone Cancer Center. Susan Johnston, Pharm.D., is Pharmaceutical Research Center Manager, UW Carbone Cancer Center, and UW Hospital and Clinics. Jill M. Kolesar, Pharm.d., is Professor of Pharmacy, School of Pharmacy, UW, and Faculty Supervisor, Analytical Laboratory for Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics, UW Carbone Cancer Center.
authors.forename: Amye J
authors.initials: AJ
authors.lastname: Tevaarwerk
authors.affiliation: Kari B. Wisinski, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, University of Wisconsin (UW), Madison, and Assistant Professor, UW Carbone Cancer Center, Madison. Colby A. Cantu, B.S., is Medical Student, School of Medicine and Public Health, UW. Jens Eickhoff, Ph.D., is Senior Scientist, Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, UW. Kurt Osterby, B.S., is Senior Decision Support Analyst, UW Hospital and Clinics, Madison. Amye J. Tevaarwerk, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, UW, and Assistant Professor, UW Carbone Cancer Center. Jennifer Heideman, R.N., is Program Manager, School of Medicine and Public Health, UW, and Program Manager, UW Carbone Cancer Center. Glenn Liu, M.D., is Associate Professor of Medicine, School of Medicine and Public Health, UW, and UW Carbone Cancer Center. George Wilding, M.D., is Professor of Medicine, School of Medicine and Public Health, UW, and Professor, UW Carbone Cancer Center. Susan Johnston, Pharm.D., is Pharmaceutical Research Center Manager, UW Carbone Cancer Center, and UW Hospital and Clinics. Jill M. Kolesar, Pharm.d., is Professor of Pharmacy, School of Pharmacy, UW, and Faculty Supervisor, Analytical Laboratory for Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics, UW Carbone Cancer Center.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Heideman
authors.affiliation: Kari B. Wisinski, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, University of Wisconsin (UW), Madison, and Assistant Professor, UW Carbone Cancer Center, Madison. Colby A. Cantu, B.S., is Medical Student, School of Medicine and Public Health, UW. Jens Eickhoff, Ph.D., is Senior Scientist, Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, UW. Kurt Osterby, B.S., is Senior Decision Support Analyst, UW Hospital and Clinics, Madison. Amye J. Tevaarwerk, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, UW, and Assistant Professor, UW Carbone Cancer Center. Jennifer Heideman, R.N., is Program Manager, School of Medicine and Public Health, UW, and Program Manager, UW Carbone Cancer Center. Glenn Liu, M.D., is Associate Professor of Medicine, School of Medicine and Public Health, UW, and UW Carbone Cancer Center. George Wilding, M.D., is Professor of Medicine, School of Medicine and Public Health, UW, and Professor, UW Carbone Cancer Center. Susan Johnston, Pharm.D., is Pharmaceutical Research Center Manager, UW Carbone Cancer Center, and UW Hospital and Clinics. Jill M. Kolesar, Pharm.d., is Professor of Pharmacy, School of Pharmacy, UW, and Faculty Supervisor, Analytical Laboratory for Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics, UW Carbone Cancer Center.
authors.forename: Glenn
authors.initials: G
authors.lastname: Liu
authors.affiliation: Kari B. Wisinski, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, University of Wisconsin (UW), Madison, and Assistant Professor, UW Carbone Cancer Center, Madison. Colby A. Cantu, B.S., is Medical Student, School of Medicine and Public Health, UW. Jens Eickhoff, Ph.D., is Senior Scientist, Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, UW. Kurt Osterby, B.S., is Senior Decision Support Analyst, UW Hospital and Clinics, Madison. Amye J. Tevaarwerk, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, UW, and Assistant Professor, UW Carbone Cancer Center. Jennifer Heideman, R.N., is Program Manager, School of Medicine and Public Health, UW, and Program Manager, UW Carbone Cancer Center. Glenn Liu, M.D., is Associate Professor of Medicine, School of Medicine and Public Health, UW, and UW Carbone Cancer Center. George Wilding, M.D., is Professor of Medicine, School of Medicine and Public Health, UW, and Professor, UW Carbone Cancer Center. Susan Johnston, Pharm.D., is Pharmaceutical Research Center Manager, UW Carbone Cancer Center, and UW Hospital and Clinics. Jill M. Kolesar, Pharm.d., is Professor of Pharmacy, School of Pharmacy, UW, and Faculty Supervisor, Analytical Laboratory for Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics, UW Carbone Cancer Center.
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.affiliation: Kari B. Wisinski, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, University of Wisconsin (UW), Madison, and Assistant Professor, UW Carbone Cancer Center, Madison. Colby A. Cantu, B.S., is Medical Student, School of Medicine and Public Health, UW. Jens Eickhoff, Ph.D., is Senior Scientist, Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, UW. Kurt Osterby, B.S., is Senior Decision Support Analyst, UW Hospital and Clinics, Madison. Amye J. Tevaarwerk, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, UW, and Assistant Professor, UW Carbone Cancer Center. Jennifer Heideman, R.N., is Program Manager, School of Medicine and Public Health, UW, and Program Manager, UW Carbone Cancer Center. Glenn Liu, M.D., is Associate Professor of Medicine, School of Medicine and Public Health, UW, and UW Carbone Cancer Center. George Wilding, M.D., is Professor of Medicine, School of Medicine and Public Health, UW, and Professor, UW Carbone Cancer Center. Susan Johnston, Pharm.D., is Pharmaceutical Research Center Manager, UW Carbone Cancer Center, and UW Hospital and Clinics. Jill M. Kolesar, Pharm.d., is Professor of Pharmacy, School of Pharmacy, UW, and Faculty Supervisor, Analytical Laboratory for Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics, UW Carbone Cancer Center.
authors.forename: Susan
authors.initials: S
authors.lastname: Johnston
authors.affiliation: Kari B. Wisinski, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, University of Wisconsin (UW), Madison, and Assistant Professor, UW Carbone Cancer Center, Madison. Colby A. Cantu, B.S., is Medical Student, School of Medicine and Public Health, UW. Jens Eickhoff, Ph.D., is Senior Scientist, Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, UW. Kurt Osterby, B.S., is Senior Decision Support Analyst, UW Hospital and Clinics, Madison. Amye J. Tevaarwerk, M.D., is Assistant Professor of Medicine, School of Medicine and Public Health, UW, and Assistant Professor, UW Carbone Cancer Center. Jennifer Heideman, R.N., is Program Manager, School of Medicine and Public Health, UW, and Program Manager, UW Carbone Cancer Center. Glenn Liu, M.D., is Associate Professor of Medicine, School of Medicine and Public Health, UW, and UW Carbone Cancer Center. George Wilding, M.D., is Professor of Medicine, School of Medicine and Public Health, UW, and Professor, UW Carbone Cancer Center. Susan Johnston, Pharm.D., is Pharmaceutical Research Center Manager, UW Carbone Cancer Center, and UW Hospital and Clinics. Jill M. Kolesar, Pharm.d., is Professor of Pharmacy, School of Pharmacy, UW, and Faculty Supervisor, Analytical Laboratory for Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics, UW Carbone Cancer Center.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Kolesar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D065693:Cytochrome P-450 Enzyme Inducers / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D018579:Patient Selection; D019338:Polypharmacy; D015995:Prevalence; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D065693:Cytochrome P-450 Enzyme Inducers; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System