Baseline requirements for novel agents being considered for phase II/III brain cancer efficacy trials: Conclusions from the Adult Brain Tumor Consortium's first workshop on CNS drug delivery

The primary message from this ABTC workshop is that significant improvements in the survival of patients with glioblastoma will likely require that tumoricidal or biologically active concentrations of therapeutic agents be achieved in non-contrast-enhancing tumor-bearing regions of the brain (Table 1). Each portion of this statement presents novel challenges and tasks for preclinical and phase I investigators that have been largely overlooked in the development of brain tumor trials. The use of these more rigorous drug delivery evaluations will encourage preclinical and phase I investigators to determine a therapeutic concentration for each agent under study and to carefully define the CNS penetration of new drugs. The results of these studies, when coupled with the standard documentation of substantial survival improvements in animal models and/or sustained clinical benefit in patients, should improve: (i) the selection of therapeutic agents being tested in future efficacy trials and (ii) the likelihood of genuinely prolonging survival in patients with these difficult-to-treat malignancies.