Glioblastoma multiforme is the most aggressive form of brain tumor. It usually occurs in patients in their 60s and is somewhat more common in males than females. Patients characteristically present with headache, nausea, muscle weakness, or personality changes. The diagnosis is generally established at the time of CT scan or MRI. Glioblastoma is the most advanced and aggressive form of astrocytoma. Grade 1 and 2 astrocytomas can often be surgically managed. Grade 3 and 4 astrocytomas are more aggressive and difficult to resect for cure. Grade 4 astrocytoma or glioblastoma is characteristically managed with a combination of surgery, radiation, and chemotherapy.
The cause of brain tumors remains unknown. There are predispositions to brain tumors associated with certain familial syndromes such as neurofibromatosis and DNA-repair deficiencies, most of these cancers arise from unknown causes. Breakthroughs in the lower grade gliomas have led to the use of drugs that block a metabolic pathway known as isocitrate dehydrogenase. Glioblastomas, however, are more rarely associated with this genetic abnormality.
Current Research Focus
The current focus in developmental therapeutics has pursued two principal areas, one immunotherapy as described; and the second, signal transduction inhibitors like C-MET, IDH, and vascular signaling.
In the interim, newer techniques for the delivery of radiation, the application of radio magnetic fields like Optune, the exploration of blood-brain barrier disrupting agents, the development of new antivascular therapies, and combinations of these modalities are often new hope for many patients.
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Following initial surgery, radiation and chemotherapy, most patients are maintained on Temozolomide treatment. Recurrent disease can be treated with antivascular agents, as these tumors are frequently highly vascular. More recently, the use of immunotherapies has led to the development of checkpoint inhibitors with or without other immunologic agents. Although responses occur in 10-20% of patients, the stable disease has also been observed and immunotherapy represents an important new direction for the treatment of this malignancy.
Although Temozolomide is the most widely used agent in this disease, a number of chemotherapy drugs have activity in glioblastoma including the mustard alkylator, of which nitrogen mustard has previously been used; Procarbazine, an oral form of the alkylating agent; Carboplatin and Topotecan.
Investigators at Duke University have utilized Irinotecan and combinations of Irinotecan with Avastin have been reported.