title: Phase I clinical trial outcomes in 93 patients with brain metastases: the MD anderson cancer center experience.
abstract: OBJECTIVE
  Patients with brain metastases are often excluded from clinical trials, but it is unclear whether they pose an enhanced risk.
  
  
  METHODS
  We reviewed the records of 1,181 consecutive patients, with and without brain metastases, treated in our Phase I Clinical Trials Program.
  
  
  RESULTS
  Ninety-three patients had brain metastases at the time of referral. Their median age was 54 years; median follow-up, 8 months. The rates of stable disease ≥ 4 months, partial response, and complete response combined in patients with and without brain metastases were 17% and 27%, respectively (P = 0.03). Although the median survival of patients with brain metastases was shorter than that of patients without brain metastases (7.5 vs. 10.3 months; P = 0.002), in multivariate analysis, the presence of brain metastases was not an independent factor predicting survival. There was no difference in time-to-treatment failure (1.74 vs. 1.84 months, respectively; P = 0.61) or in grade 3 and 4 toxicity rates (including neurologic; 12% vs. 10%, respectively; P = 0.77) between patients with and without brain metastases.
  
  
  CONCLUSIONS
  The rates of survival and response of patients with brain metastases were lower than those for other patients in the phase I setting, but the presence of brain metastases was not an independent prognostic factor predicting survival, indicating that other covariates that coexist with brain metastases were more significant. Time-to-treatment failure for patients with brain metastases was not decreased, nor was the incidence of serious adverse effects (including neurologic toxicity) increased, suggesting that these patients should be eligible for early clinical trials.
authors.affiliation: Investigational Cancer Therapeutics and Quantitative Sciences Division, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. atsimber@mdanderson.org
authors.forename: Apostolia Maria
authors.initials: AM
authors.lastname: Tsimberidou
authors.forename: Katherine
authors.initials: K
authors.lastname: Letourneau
authors.forename: Sijin
authors.initials: S
authors.lastname: Wen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wheler
authors.forename: David
authors.initials: D
authors.lastname: Hong
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Iskander
authors.forename: Cynthia
authors.initials: C
authors.lastname: Uehara
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D002648:Child; D017321:Clinical Trials, Phase I as Topic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents