Why are some children excluded from many early-phase clinical trials a priori?
The final area of controversy in this discussion involves the historical exclusion of pediatric patients with tumors of the central nervous system (CNS), brain metastases, or leukemia from participating in early-phase trials. The rationale for this has been based on the assumption that patients with CNS tumors or brain metastases are neurologically unstable, thus compromising the ability to assess the neurotoxicity of a new agent. In addition, since many of these patients were previously taking enzyme-inducing anticonvulsant agents, there were concerns regarding altered drug metabolism of the experimental agent. Fortunately, with the advent of newer generations of anti-convulsants that do not substantially affect metabolism through the cytochrome p450 system, this particular concern has become obsolete. In fact, we have found that actively including patients with CNS tumors does not compromise the goals of an early-phase study, as these patients have often received only surgery or radi
