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Biotin Improves Radiotherapy for Glioblastoma Multiforme Brain Tumors

Glioblastoma multiforme (GBM) is a fast-growing malignant brain tumor. Traditional treatment for GBM typically involves surgery, external beam radiotherapy (EBRT), and possibly chemotherapy. EBRT has proven to be the most effective therapeutic partner to surgical removal of the neoplasm, and is the focus of much research in an effort to increase its efficacy. In addition, radio-immunotherapy - the combination of antitumor antibodies and radiation - is being investigated as an option.36

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However, there are many obstacles to applying and accumulating the antibodies in these brain malignancies, including:36

  • Crossing the blood-brain barrier.
  • Inconsistent expression of antigens.
  • Limited blood supply in the tumor.
  • Necrosis and/or fibrosis.

Because of these factors, the amount of antibodies that manages to accumulate in GBM brain tumors is less than 0.01% of total antibodies given per gram of tumor tissue. In an effort to improve radio-immunotherapy treatment of GBM malignancies, researchers have utilized the avidin/biotin system to pre-target the tumor with anti-tenascin antibodies attached to radioactively labeled biotin molecules. Applied locoregionally, studies show that anti-tenascin effectively targets tenascin, a specific antigen protein on cell walls of the tumor stroma. Once bound to the tenascin proteins, the radioactive molecules destroy the tumor cells (including surrounding antigen-negative tumor cells).36

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In one study involving 73 patients with recurrent GBM, radio-immunotherapy utilizing avidin/biotin pre-targeting demonstrated very favorable results compared to other treatments. Of note is that the majority of the 73 patients entered the study with only partial surgical success, and none of these achieved a complete response to adjuvant radiotherapy given prior to the study. Despite these poor prognostic indicators entering the study, 75% of the participants experienced disease stabilization and markedly better responses in terms of both overall and progression-free survival times (17.5 and 5 months) than surgery and radiotherapy (3.5-17 and 3.5 months). These outcomes were improved even more when combined with the alkylating drug Temodar®, with 25 months overall survival rate and 10 months with no progression of the cancer.36

Results of another non-randomized clinical trial involving 37 patients with high-grade glioma (17 had grade III glioma and 20 had GBM) also supports the improved tumor response from using the avidin/biotin pre-targeting approach - including over systemic or locally applied antibodies (without the avidin/biotin). Deemed disease-free after receiving surgery and radiotherapy, 19 of the 37 patients were given pre-targeted radio-immunotherapy within one month of radiotherapy. The responses from the test group were remarkable in terms of median disease-free and overall survival, as compared to the control group patients:37


  Treated Group (19) Untreated Control Group (18)
GBM Glioma GBM (12) Glioma
Median Disease Free Interval 28 months 56 months (failed to comply with check-ups) (failed to comply with check-ups)
Median Overall Survival 33.5 months (one still without evidence of disease) 56 months (estimated; cannot be calculated since only 2 died) 8 months 33 months
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Localized tissue death.6
Thickened, scarred connective tissue.6
A protein in egg whites.9
Tenascin, an extracellular matrix glycoprotein over-produced in the tumor stroma.36
The structures that connect the tumor to normal tissue.6, 36
Temozolomide.36
 
 
 
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