Gene therapy opens promising alternative in the treatment of primary malignant brain tumors

GlioblastomaGene therapy to protect blood stem cells from chemotherapy allows more intensive treatment of patients with glioblastoma, researchers say.

“We developed a strategy to successfully shield the marrow and blood cells and thus patients can now get this drug combination with benzylguanine and temozolomide while the marrow and blood cells are protected and shielded,” Dr. Hans-Peter Kiem from Fred Hutchinson Cancer Research Center in Seattle told Reuters Health by email.

“MGMT (methylguanine methyltransferase) in the tumor will inactivate the chemotherapy and thus make the tumor insensitive to chemotherapy,” Dr. Kiem explained. “We can reverse this by disabling MGMT and making the tumor again sensitive to temozolomide using a drug called benzylguanine. Unfortunately disabling MGMT in blood and marrow cells makes them also more sensitive to temozolomide causing low blood counts and preventing the use of this approach.”

[Read more…]

No Benefit From Dose-Dense Chemo in Glioblastoma

GlioblastomaIntensified chemoradiation with temozolomide for newly diagnosed glioblastoma failed to improve survival or slow disease progression, according to results of a randomized trial.

Patients randomized to conventional treatment with radiation therapy and temozolomide (Temodar) had a median overall survival (OS) of 16.6 months, whereas patients who received radiation and dose-dense temozolomide had a median survival of 14.9 months.

Median progression-free survival (PFS) was about a month longer with the dose-dense regimen, but the difference did not reach statistical significance, reported Mark R. Gilbert, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues online in the Journal of Clinical Oncology.

“This study did not demonstrate improved efficacy for dose-dense temozolomide for newly diagnosed glioblastoma multiforme, regardless of [MGMT] methylation status,” the authors concluded. “However, it did confirm the prognostic significance of MGMT (methylguanine-DNA methyltransferase) methylation. Feasibility of large-scale accrual, prospective tumor collection, and molecular stratification was demonstrated.”

[Read more…]

Current Treatment Options in Adult Glioblastoma

a report by Christopher E Pelloski, MD1 and Mark R Gilbert, MD2

1. Assistant Professor, Departments of Radiation Oncology and Pathology; 2. Professor and Deputy Chair, Department of Neuro-oncology, University of Texas MD Anderson Cancer Center

The purpose of this article is to review the current treatment options for patients with glioblastoma (GBM). The current standard of care involves maximal safe surgical resection followed by concurrent chemotherapy with radiation followed by adjuvant chemotherapy. Although level 1 evidence supports the use of this treatment, GBM remains incurable and most patients will succumb to the disease within two years of diagnosis. The need for better treatments has led to the development of numerous experimental agents that are currently in various phases of pre-clinical and clinical application. The new treatment approaches provide hope that significant treatment advances are likely, but will require a collaborative effort between laboratory-based and clinical investigators. [Read more…]

State-of-the-art Therapy for Glioblastoma Multiforme

a report by Henry S Friedman, MD

James B Powell Jr Professor of Neuro-oncology, Dukes University Medical Center

The treatment of patients with glioblastoma multiforme (GBM) is conventionally considered to be a palliative venture with no hope of cure. Traditionally, patients are treated with maximal surgical resection based on the premise that, although surgery is not a curative procedure, a major resection provides for a longer survival and better quality of life.1 Radiotherapy increases the duration of survival, but again is not a curative intervention.2 The role of chemotherapy, specifically focusing on a foundation of chloroethylating agents such as carmustine (BCNU) or lomustine (CCNU), has been controversial with an equal number of clinicians arguing in favor of or against this treatment. Meta-analysis makes it clear that there is a small increase in median survival associated with the addition of these agents, but a consensus was never reached regarding their use.3 [Read more…]

Glioblastoma Multiforme—Past, Present, and Future

The most common cancer arising from the brain is the glioblastoma multiforme (GBM). It is also the most deadly,1 representing the most aggressive subtype among the gliomas, a collection of tumors including astrocytomas and oligodendrogliomas. In 1926, Bailey and Cushing, in describing ‘spongioblastoma multiforme’, the label then used for GBM, noted that:

“It is from this group doubtless that the generally unfavorable impression regarding gliomas as a whole has been gained. It is not only the largest single group in the series…but at the same time is one of the most malignant…In the five unoperated cases, the average duration of life from the onset of symptoms was only three months, which speaks well on the whole for the average survival period of twelve months for those surgically treated. [Read more…]