title: Risks and benefits of phase 1 oncology trials, 1991 through 2002.
abstract: BACKGROUND
  Previous reviews of phase 1 oncology trials reported a rate of response to treatment of 4 to 6 percent and a toxicity-related death rate of 0.5 percent. These results may not reflect the rates in current phase 1 oncology trials.
  
  
  METHODS
  We reviewed all nonpediatric phase 1 oncology trials sponsored by the Cancer Therapy Evaluation Program at the National Cancer Institute between 1991 and 2002. We report the rates of response to treatment, of stable disease, of grade 4 toxic events, and of treatment-related deaths.
  
  
  RESULTS
  We analyzed 460 trials involving 11,935 participants, all of whom were assessed for toxicity and 10,402 of whom were assessed for a response to therapy. The overall response rate (i.e., for both complete and partial responses) was 10.6 percent, with considerable variation among trials. "Classic" phase 1 trials of single investigational chemotherapeutic agents represented only 20 percent of the trials and had a response rate of 4.4 percent. Studies that included at least one anticancer agent approved by the Food and Drug Administration constituted 46.3 percent of the trials and had a response rate of 17.8. An additional 34.1 percent of participants had stable disease or a less-than-partial response. The overall rate of death due to toxic events was 0.49 percent. Of 3465 participants for whom data on patient-specific grade 4 toxic events were available, 14.3 percent had had at least one episode of grade 4 toxic events.
  
  
  CONCLUSIONS
  Overall response rates among phase 1 oncology trials are higher than previously reported, although they have not changed for classic phase 1 trials, and toxicity-related death rates have remained stable. Rates of response and toxicity vary, however, among the various types of phase 1 oncology trials.
authors.affiliation: Department of Clinical Bioethics, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Md 20892-1156, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Horstmann
authors.forename: Mary S
authors.initials: MS
authors.lastname: McCabe
authors.forename: Louise
authors.initials: L
authors.lastname: Grochow
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Larry
authors.initials: L
authors.lastname: Rubinstein
authors.forename: Troy
authors.initials: T
authors.lastname: Budd
authors.forename: Dale
authors.initials: D
authors.lastname: Shoemaker
authors.forename: Ezekiel J
authors.initials: EJ
authors.lastname: Emanuel
authors.forename: Christine
authors.initials: C
authors.lastname: Grady
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D015316:Genetic Therapy / Q000009:adverse effects; D006801:Humans; D009369:Neoplasms / Q000401:mortality / Q000628:therapy*; D017063:Outcome Assessment, Health Care; D012189:Retrospective Studies; D018570:Risk Assessment
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines