It Is Time to Include Patients With Brain Tumors in Phase I Trials in Oncology

Traditionally,themajorityofphaseIstudiesofnovelagentsin oncology have excluded patients with primary brain tumors. Although phase I studies are designed to determine optimal dosing, efficacy data are increasingly used to look for a signal in particular tumors. Excluding patients with primary brain tumors from phase I studies results in a significant handicap in the identification of drugs that may be particularly active in these tumor types. In this era of targeted therapies, we suggest that the reasons for excluding these patients are largely obsolete. It is time to reconsider this practice and include patients with brain tumors in phase I trials in oncology. Several reasons are given for the exclusion of patients with brain tumors from phase I trials. First, patients with brain tumors were historically treated with cytochrome P450 enzyme-inducing antiepileptic drugs (EIAEDs), such as phenytoin and carbamazepine, which potentially accelerated hepatic metabolism of the agent under study. Asaresult,aseparatephaseIstudywasoftenrequiredforpatientswith