title: Risk of serious toxicity in 1181 patients treated in phase I clinical trials of predominantly targeted anticancer drugs: the M. D. Anderson Cancer Center experience.
abstract: BACKGROUND
  This study assessed toxicity in advanced cancer patients treated in a phase I clinic that focuses on targeted agents.
  
  
  METHODS
  An analysis of database records of 1181 consecutive patients with advanced cancer who were treated in the phase I program starting 1 January 2006 was carried out.
  
  
  RESULTS
  All patients were treated on at least 1 of the 82 phase I clinical trials. Overall, 56 trials (68.3%) had only targeted agents, 13 (15.9%) only cytotoxics, and 13 (15.9%) targeted and cytotoxic agents. Rates of grade 3 and 4 toxicity that were at least possibly drug related were 7.1% and 3.2%, respectively, and 5 of the 1181 patients (0.4%) died from toxicity that was at least possibly drug related. The most common grade 3 or more toxic effects were neutropenia, thrombocytopenia, anemia, dehydration, infection, altered mental status, bleeding, vomiting, nausea, and diarrhea. Eastern Cooperative Oncology Group (ECOG) performance status greater than zero and use of a cytotoxic agent were selected as independent factors associated with serious toxicity.
  
  
  CONCLUSIONS
  Phase I trials of primarily targeted agents showed low rates of toxicity, with 10.3% of patients experiencing grade 3 or 4 toxicity and a 0.4% rate of death, at least possibly drug related.
authors.affiliation: Departments of Investigational Cancer Therapeutics-a Phase I Clinical Trials Program. Electronic address: jjwheler@mdanderson.com.
authors.forename: J J
authors.initials: JJ
authors.lastname: Wheler
authors.affiliation: Departments of Investigational Cancer Therapeutics-a Phase I Clinical Trials Program.
authors.forename: A M
authors.initials: AM
authors.lastname: Tsimberidou
authors.affiliation: Departments of Investigational Cancer Therapeutics-a Phase I Clinical Trials Program.
authors.forename: D S
authors.initials: DS
authors.lastname: Hong
authors.affiliation: Departments of Investigational Cancer Therapeutics-a Phase I Clinical Trials Program.
authors.forename: A
authors.initials: A
authors.lastname: Naing
authors.affiliation: Departments of Investigational Cancer Therapeutics-a Phase I Clinical Trials Program.
authors.forename: G S
authors.initials: GS
authors.lastname: Falchook
authors.affiliation: Departments of Investigational Cancer Therapeutics-a Phase I Clinical Trials Program.
authors.forename: S
authors.initials: S
authors.lastname: Fu
authors.affiliation: Departments of Investigational Cancer Therapeutics-a Phase I Clinical Trials Program; Breast Medical Oncology.
authors.forename: S
authors.initials: S
authors.lastname: Moulder
authors.affiliation: Departments of Investigational Cancer Therapeutics-a Phase I Clinical Trials Program.
authors.forename: B
authors.initials: B
authors.lastname: Stephen
authors.affiliation: Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, USA.
authors.forename: S
authors.initials: S
authors.lastname: Wen
authors.affiliation: Departments of Investigational Cancer Therapeutics-a Phase I Clinical Trials Program.
authors.forename: R
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D017321:Clinical Trials, Phase I as Topic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D009369:Neoplasms / Q000188:drug therapy*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents