title: Preclinical Data on Efficacy of 10 Drug-Radiation Combinations: Evaluations, Concerns, and Recommendations.
abstract: BACKGROUND
  Clinical testing of new therapeutic interventions requires comprehensive, high-quality preclinical data. Concerns regarding quality of preclinical data have been raised in recent reports. This report examines the data on the interaction of 10 drugs with radiation and provides recommendations for improving the quality, reproducibility, and utility of future studies. The drugs were AZD6244, bortezomib, 17-DMAG, erlotinib, gefitinib, lapatinib, oxaliplatin/Lipoxal, sunitinib (Pfizer, Corporate headquarters, New York, NY), thalidomide, and vorinostat.
  
  
  METHODS
  In vitro and in vivo data were tabulated from 125 published papers, including methods, radiation and drug doses, schedules of administration, assays, measures of interaction, presentation and interpretation of data, dosimetry, and conclusions.
  
  
  RESULTS
  In many instances, the studies contained inadequate or unclear information that would hamper efforts to replicate or intercompare the studies, and that weakened the evidence for designing and conducting clinical trials. The published reports on these drugs showed mixed results on enhancement of radiation response, except for sunitinib, which was ineffective.
  
  
  CONCLUSIONS
  There is a need for improved experimental design, execution, and reporting of preclinical testing of agents that are candidates for clinical use in combination with radiation. A checklist is provided for authors and reviewers to ensure that preclinical studies of drug-radiation combinations meet standards of design, execution, and interpretation, and report necessary information to ensure high quality and reproducibility of studies. Improved design, execution, common measures of enhancement, and consistent interpretation of preclinical studies of drug-radiation interactions will provide rational guidance for prioritizing drugs for clinical radiotherapy trials and for the design of such trials.
authors.affiliation: Radiation Research Program, National Cancer Institute, 9609 Medical Center Dr, Rockville, 20850, MSC 9727.
authors.forename: Helen B
authors.initials: HB
authors.lastname: Stone
authors.affiliation: Radiation Research Program, National Cancer Institute, 9609 Medical Center Dr, Rockville, 20850, MSC 9727. Electronic address: bernhardej@mail.nih.gov.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Bernhard
authors.affiliation: Radiation Research Program, National Cancer Institute, 9609 Medical Center Dr, Rockville, 20850, MSC 9727.
authors.forename: C Norman
authors.initials: CN
authors.lastname: Coleman
authors.affiliation: Radiation Research Program, National Cancer Institute, 9609 Medical Center Dr, Rockville, 20850, MSC 9727.
authors.forename: James
authors.initials: J
authors.lastname: Deye
authors.affiliation: Radiation Research Program, National Cancer Institute, 9609 Medical Center Dr, Rockville, 20850, MSC 9727.
authors.forename: Jacek
authors.initials: J
authors.lastname: Capala
authors.affiliation: Radiation Biology Branch, National Cancer Institute, MSC 1002, 10 Center Dr, Bethesda, MD, 20892.
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
authors.affiliation: Stanford University, Radiation and Cancer Biology, CCSR-S Rm 1255, 269 Campus Dr, Stanford, CA, 94305.
authors.forename: J Martin
authors.initials: JM
authors.lastname: Brown