title: Eligibility of patients with brain metastases for phase I trials: time for a rethink?
abstract: Since the inception of phase I clinical trials in cancer, patients with symptomatic brain metastases have commonly been excluded from participation because of a poor outlook. However, patients with asymptomatic brain metastases pose an increasingly frequent challenge for clinicians: more sensitive brain imaging can identify clinically silent brain metastases; frequency of detection might have increased because of changes in the natural history of many tumour types as a result of more effective systemic treatment; and routine brain imaging as a screening procedure before entry into a clinical trial can show lesions which are of questionable clinical importance, but which frequently preclude trial enrolment. Evidence suggests that delaying whole-brain radiotherapy until symptomatic progression has no adverse effect on prognosis. Safety and efficacy data are accumulating for targeted agents to treat brain metastases. We think that a subset of patients with asymptomatic brain metastases might be appropriately entered into phase I trials, and we present our approach for their stratification. As a consequence, patients might have increased access to experimental treatments and thus effective interventions for brain metastases might be developed more promptly.
authors.affiliation: Drug Development Unit, Royal Marsden Hospital, Downs Road, Sutton, Surrey, UK.
authors.forename: Craig P
authors.initials: CP
authors.lastname: Carden
authors.forename: Roshan
authors.initials: R
authors.lastname: Agarwal
authors.forename: Frank
authors.initials: F
authors.lastname: Saran
authors.forename: Ian R
authors.initials: IR
authors.lastname: Judson
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary*; D017321:Clinical Trials, Phase I as Topic; D016371:Cranial Irradiation / Q000009:adverse effects; D004608:Eligibility Determination; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D018579:Patient Selection; D014057:Tomography, X-Ray Computed