Editorial Neuro - oncology clinical trials : Promise and pitfalls


The treatment of malignant neoplasms involving the central nervous system, from either primary or metastatic cancer, remains inadequate. Despite intensive efforts in laboratory and clinical investigations, the prognosis for patients with involvement of the central nervous system remains grim. For example, patients with glioblastoma multiforme have a median survival of less than one year, similar to that reported in 1980 [1]. Similarly, patients with metastatic lesions from systemic cancer continue to do poorly unless the lesions are few in number (3 or less) and are amenable to both local (surgical removal or radiosurgery) and whole brain radiotherapy [2]. Clearly, significant advances are needed in the treatment of malignant brain tumors. There has been great interest in developing chemo-therapy-based treatment strategies for brain tumors, focusing mainly on primary glial neoplasms (i.e., ana-plastic astrocytoma and glioblastoma multiforme). Early investigations into the biology of these tumors recognized that the lesions are extremely heterogeneous. These tumors form a solid distinct mass that is easily visible using current imaging modalities. However, pathologic evaluations reveal significant infiltration of the surrounding brain parenchyma by tumor cells, detectable only by microscopic examination [3]. Imaging studies of this area, often referred to a 'brain-around-tumor' (BAT), show either edema or normal appearing paren-chyma. Conversely, brain metastases usually exhibit clear delineation between tumor and surrounding normal brain. Malignant brain tumors, both primary and metastatic, are typically enhancing on imaging studies, indicating blood-brain barrier dysfunction in the region. The enhancing region encompasses the entire metastases, but glial neoplasms have a non-enhancing, infiltrating component present in the surrounding brain parenchyma, in which the blood-brain barrier remains functional. Therefore, despite pathologic differences in regional infiltration of tumor, patients with infiltrating glial malig-nancies, and those with multiple brain metastases, have a common need for a treatment that encompasses a large portion of the brain. For this reason, external beam radiotherapy is the standard treatment for both types of central nervous system cancers. Although proven to be efficacious, radiation therapy is not curative and recurrent tumor is a frequent occurrence, which has elicited great interest in developing chemotherapy strategies for recurrent cancers. Three manuscripts in this journal describe studies using the chemotherapy agent, temozolo-mide, for recurrent malignant gliomas and recurrent brain metastases [4-6]. This enthusiasm stems from several factors: temozolomide is an oral agent; has a low incidence of side-effects, non-cumulative myelotoxicity; and crosses the blood-brain barrier [7]. Additionally, pharmacokinetic studies indicate that the metabolism of …

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@inproceedings{Gilbert2005EditorialN, title={Editorial Neuro - oncology clinical trials : Promise and pitfalls}, author={Mark Gilbert}, year={2005} }