Brain Cancer

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.

During the past 18 months, researchers have developed substantial evidence supporting the notion that stem cells play a critical role in the development of at least some cancers, their progression, and the prognosis of patients, including breast, brain, lung, and prostate cancer, multiple myeloma, and melanoma.

Brain metastases from renal cell carcinoma (RCC) cause significant morbidity and mortality. More effective treatment approaches are needed. Traditionally, whole-brain radiotherapy has been used for palliation. With advances in radiation oncology, stereotactic radiosurgery and hypofractionated stereotactic radiotherapy have been utilized for RCC brain metastases, producing excellent outcomes. This review details the role of radiotherapy in various subgroups of patients with RCC brain metastases as well as the associated toxicities and outcomes. Newer radiosensitizers (eg, motexafin gadolinium [Xcytrin]) and chemotherapeutic agents (eg, temozolomide [Temodar]) used in combination with radiotherapy will also be discussed.

Brain metastases from renal cell carcinoma (RCC) cause significant morbidity and mortality. More effective treatment approaches are needed. Traditionally, whole-brain radiotherapy has been used for palliation. With advances in radiation oncology, stereotactic radiosurgery and hypofractionated stereotactic radiotherapy have been utilized for RCC brain metastases, producing excellent outcomes. This review details the role of radiotherapy in various subgroups of patients with RCC brain metastases as well as the associated toxicities and outcomes. Newer radiosensitizers (eg, motexafin gadolinium [Xcytrin]) and chemotherapeutic agents (eg, temozolomide [Temodar]) used in combination with radiotherapy will also be discussed.

After 2 decades of minimal progress, there have been important advances in the treatment of brain tumors with chemotherapy. A trial conducted by the European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC) recently demonstrated the benefit of radiation therapy with concomitant and adjuvant temozolomide (Temodar) chemotherapy for glioblastomas. There is also increasing evidence that chemotherapy may be beneficial for anaplastic and low-grade gliomas, as well as a variety of less common tumors.

When physicians are deciding whether to offer stereotactic radiosurgery to patients with multiple brain metastases who have a fairly good functional status, they should consider the total volume of these metastases instead of their number.

The treatment of malignant gliomashas received significant attentionover the past decade.This likely represents recognition ofthe poor prognosis associated withthese cancers combined with the challengeof developing a treatment strategyfor a neoplasm that, although itrarely metastasizes, has not proven tobe curable by surgical resection. Infact, debate continues about the roleof aggressive surgery in this disease,given that an image-guided biopsycan provide accurate diagnosis whileminimizing any procedure-relatedmorbidity and mortality. Some studieshave strongly suggested a therapeuticbenefit with surgical resection,but the extent of resection is a criticalcomponent.