Phase I clinical trial outcomes in 93 patients with brain metastases: the MD anderson cancer center experience. Clin Cancer Res 2011 Jun 15;17(12):4110-8
Date
03/19/2011Pubmed ID
21415223Pubmed Central ID
PMC3410654DOI
10.1158/1078-0432.CCR-10-3095Scopus ID
2-s2.0-79959268009 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
PURPOSE: Patients with brain metastases are often excluded from clinical trials, but it is unclear whether they pose an enhanced risk.
EXPERIMENTAL DESIGN: 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.
Author List
Tsimberidou AM, Letourneau K, Wen S, Wheler J, Hong D, Naing A, Iskander NG, Uehara C, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Antineoplastic Agents
Brain Neoplasms
Child
Clinical Trials, Phase I as Topic
Female
Humans
Male
Middle Aged
Molecular Targeted Therapy
Retrospective Studies
Survival Analysis
Time Factors
Treatment Outcome
Young Adult
