Brain Cancer

The odds are exceedingly slim that you'll ever see an intracranial MPNST. With no established treatments and tough clinical dilemmas, you don't want to. But 3 recent case reviews and new insights from biology suggest this rare tumor may finally be vulnerable.

Typically glioblastoma patients are dead within 15 months of diagnosis, no matter how complete and well-planned their therapy.

The Ivy Glioblastoma Atlas Project will track genetic mutations in glioblastoma multiforme and produce a free, online medical atlas. The Seattle-based project is a partnership between the Ben and Catherine Ivy Foundation, the Allen Institute for Brain Science, and the Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment at the Swedish Neuroscience Institute.

In July 2009, the US Food and Drug Administration (FDA) granted approval for use of the vascular endothelial growth factor (VEGF) inhibitor bevacizumab (Avastin) in combination with interferon alfa for treatment of patients with metastatic renal cell carcinoma (RCC).

Adult survivors of childhood craniopharyngiomas, the second most common type of childhood brain tumor, face many challenges, including multiple life-threatening metabolic abnormalities. Serious metabolic deficits can result from injury to the pituitary gland or hypothalamus.

The development of metastatic disease in patients with paraganglioma is an unusual and challenging event. This case report and review describes the specific features of this disease and the multiple therapeutic options.

Despite the high prevalence of brain metastases in patients with metastatic lung cancer, these patients have been excluded from enrollment in clinical trials of new therapeutic drugs. The reasons for exclusion have centered on concerns that the blood-brain barrier may impede drug delivery into brain metastases, that brain metastases confer a dismal survival for metastatic lung cancer patients, and that brain metastases carry risk for cerebrovascular hemorrhage. A focused, updated review of these issues, however, clearly shows that these particular concerns are unwarranted. An extensive review of clinical trials on the efficacy of chemotheraputic agents against lung cancer brain metastases is also provided. This collective information describes an area in need of therapeutic development and supports an initiative to evaluate novel targeted therapies for lung cancer brain metastases.

With the combination of radiation therapy and temozolomide (Temodar), some patients with glioblastoma multiforme are now surviving more than 4 years, according to updated results from a randomized phase III trial

Encouraging Avastin results in glioblastoma multiforme

Data for the investigational agent cediranib (AZD2171) were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) from a phase II monotherapy study in patients with recurrent glioblastoma, the most aggressive form of primary brain tumor, with a high unmet medical need.

Swiss drug regulators have become the first to approve Novartis' Tasigna (nilotinib) for the treatment of patients with Ph+ chronic myeloid leukemia who are resistant or intolerant to imatinib (Gleevec)

In the June issue of ONCOLOGY, authors McGregor et al did an admirable job of reviewing childhood cancer advances and current issues in their article entitled "Pediatric Cancers in the New Millennium: Dramatic Progress, New Challenges"

The oral multitargeted tyrosine kinase inhibitor cediranib (Recentin, AstraZeneca), known experimentally as AZD2171, alleviated edema and showed an improvement in progression-free survival, compared with historical controls, in a phase II study of patients with recurrent glioblastoma

The third-generation epothilone KOS-1803 may optimize tumor penetration while limiting exposure to other tissues

Radioimmunotherapy (RIT) with a radiolabeled monoclonal antibody 131I-8H9, delivered intrathecally, appears to have clinical utility when added to salvage therapy for patients with metastatic cancer to the central nervous system (CNS), according to a phase I study reported at the 2007 American Association of Cancer Research annual meeting (LB-4).

Celldex Therapeutics has initiated a multicenter phase II/III trial of its brain tumor vaccine CDX-110 in patients with newly diagnosed glioblastoma multiforme (GBM) that expresses EGFRvIII, a variant of EGFR not present in normal tissue.

Metastatic lesions to the brain occur commonly in oncology patients and portend a very poor outcome, as they often occur in the setting of progressive systemic metastatic disease and can result in neurologic deterioration that may preclude therapy. Therapy of patients with brain metastases requires a combination of measures to achieve local control at the site of metastasis (eg, with surgical resection or radiosurgery) and to reduce the subsequent risk of recurrences elsewhere in the brain (eg, with whole-brain radiation). Successful therapy of extracranial systemic metastases is required for optimal outcomes. Clinical trials are currently underway to define the optimal role of whole-brain radiation and radiosurgery in different subsets of patients. Novel therapies to enhance radiation responsiveness are also under investigation. In the current review, we discuss recent developments in the management of patients with brain metastases.

Metastatic lesions to the brain occur commonly in oncology patients and portend a very poor outcome, as they often occur in the setting of progressive systemic metastatic disease and can result in neurologic deterioration that may preclude therapy. Therapy of patients with brain metastases requires a combination of measures to achieve local control at the site of metastasis (eg, with surgical resection or radiosurgery) and to reduce the subsequent risk of recurrences elsewhere in the brain (eg, with whole-brain radiation). Successful therapy of extracranial systemic metastases is required for optimal outcomes. Clinical trials are currently underway to define the optimal role of whole-brain radiation and radiosurgery in different subsets of patients. Novel therapies to enhance radiation responsiveness are also under investigation. In the current review, we discuss recent developments in the management of patients with brain metastases.

Therapy of patients with brain metastases requires a combination of measures to achieve local control at the site of metastasis and to reduce the subsequent risk of recurrences elsewhere in the brain. In the current review, we discuss recent developments in the management of patients with brain metastases.

The National Cancer Institute (NCI) recently awarded The University of Texas M.D. Anderson Cancer Center $11 million to lead the largest genetic study ever conducted on the causes and risk factors of adult and pediatric gliomas. Melissa Bondy, PhD, professor of epidemiology and director of the Childhood Cancer Epidemiology and Prevention Center, is principal investigators of the "Gliogene" study.

A device that displays a holograph-like 3-dimensional (3D) image, created from a CT, MRI, or PET dataset, holds promise for more accurate radiotherapy treatment planning (see image on page 1). James C. H. Chu, PhD, professor of radiation oncology, Rush University Medical Center, presented results of a pilot study of the Perspecta Spatial 3D System, developed by Actuality Systems, Inc. (Bedford, Massachusetts), at the 48th Annual Meeting of the American Society for Therapeutic Radiology and Oncology

Motexafin gadolinium (MGd, Xcytrin) combined with whole brain radiation therapy (WBRT) prolongs time to neurologic progression in non-small-cell lung cancer (NSCLC) patients with brain metastases if treatment starts within 3 weeks of the brain metastasis diagnosis, according to data from a phase III trial.

Pharmacyclics, Inc, announced that new data and analyses supporting the company's decision to file a new drug application (NDA) for motexafin gadolinium (Xcytrin) were presented at the 2006 annual meeting of the American Society of Clinical Oncology (ASCO). This abstract was selected by the ASCO Scientific Program Committee to be featured in the "2006 Best of ASCO Meetings" in June.

New research shows that in order to grow, gliomas attract stem cells circulating in the blood to develop new blood vessels, as well as using blood vessels from the brain itself.

New research shows that the oncolytic reovirus, which kills cancer cells by replication within the cell, may also have the potential to prime the immune system to mount a defense against cancer cells

Brain, lung, and ovarian cancers have been chosen as the first cancers to be studied in the pilot phase of The Cancer Genome Atlas (TCGA) project

Modafinil (Provigil) significantly improved cognitive function, mood, and fatigue in patients with brain tumors in a pilot study

Childhood survivors of brain tumors who were diagnosed at age 10 or younger have worse depressive symptomatology and social skills and lower feelings of self-worth than their counterparts who were diagnosed as pre-teens or teenagers

Takeda Pharmaceutical has signed an exclusive licensing agreement with Galaxy Biotech (Mountain View, California) to develop, manufacture, and market HuL2G7, a recombinant humanized anti-hepatocyte growth factor (anti-HGF) monoclonal antibody developed by Galaxy Biotech. HGF is believed to mediate proliferation, metastasis, antiapoptosis, and neoangiogenesis of many types of tumors. In animal models, treatment of intracranial glioma xenografts with HuL2G7 induced substantial tumor regression and prolonged survival (Clin Cancer Res 12:1292-1298, 2006).

EntreMed, Inc.'s lead drug candidate Panzem (2-methoxyestradiol or 2ME2) has received orphan drug status from the FDA for the treatment of glioblastoma multiforme. In vitro studies in glioma cell lines demonstrated Panzem's antiproliferative activity, and in vivo studies in a preclinical model of glioblastoma showed its antitumor activity, EntreMed said in a press release. Panzem is currently being investigated in a phase II trial in patients with glioblastoma multiforme at the Brain Tumor Center at Duke University Medical Center. The agent previously received orphan drug designation for the treatment of multiple myeloma and ovarian cancer.