title: Ultimate fate of oncology drugs approved by the us food and drug administration without a randomized Trial.
abstract: OBJECTIVE
  To approve a new anticancer drug, the US Food and Drug Administration often requires randomized trials. However, several oncology drugs have been approved on the basis of objective end points without a randomized trial. We reviewed the long-term safety and efficacy of such agents.
  
  
  METHODS
  We searched the Web site of the US Food and Drug Administration's Center for Drug Evaluation and Research and MEDLINE for initial applications of investigational anticancer drugs from 1973 through 2006.
  
  
  RESULTS
  Overall, 68 oncology drugs, excluding hormone therapy and supportive care, were approved, including 31 without a randomized trial. For these 31 drugs, a median of two clinical trials (range, one to seven) and 79 patients (range, 40 to 413) were used per approval. Objective response was the most common end point used for approval; median response rate was 33% (range, 11% to 90%). Thirty drugs are still fully approved. United States marketing authorization for one drug, gefitinib (an epidermal growth factor receptor [EGFR] inhibitor), was rescinded after a randomized trial showed no survival improvement; however, this trial was performed in unselected patients, and it was subsequently demonstrated that patients with EGFR mutation are more likely to respond. Nineteen of the 31 drugs have additional uses (per National Comprehensive Cancer Network or National Cancer Institute Physician Data Query guidelines), and subsequent formal US Food and Drug Administration approvals were obtained for 11 of these (range, one to 18 new indications). No drug has demonstrated safety concerns.
  
  
  CONCLUSIONS
  Nonrandomized clinical trials with definitive end points can yield US Food and Drug Administration approvals, and these drugs have a reassuring record of long-term safety and efficacy.
authors.affiliation: The University of Texas M. D. Anderson Cancer Center, Department of Investigational Cancer Therapeutics, Unit 455, 1515 Holcombe Blvd, Houston, TX 77030, USA. atsimber@mdanderson.org
authors.forename: Apostolia-Maria
authors.initials: AM
authors.lastname: Tsimberidou
authors.forename: Fadi
authors.initials: F
authors.lastname: Braiteh
authors.forename: David J
authors.initials: DJ
authors.lastname: Stewart
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017277:Drug Approval / Q000379:methods*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents