Portland, Ore.
Sulfur agents can add antitoxic protection while crossing the blood-brain barrier
Researchers at Oregon Health & Science University have found a promising new technique that may increase effective chemotherapy treatment for brain and other tumors while reducing the toxic damage to the body's bone marrow. In an article to be published Nov. 1 in the journal Cancer Research, Edward Neuwelt, M.D., neurosurgeon and director of the Blood-Brain Barrier Program at OHSU, reports that certain sulfur agents introduced directly into the lower circulatory system can protect bone marrow from damage while chemotherapy is sent to the brain.
While the published study was done in rat models, Neuwelt and co-workers already have enrolled patients in a clinical trial.
"This is a further step in the evolution of medicine to deliver increased doses of drugs safely and effectively across the blood-brain barrier to brain tumors," said Neuwelt. "While we've experienced success treating brain tumors in the past, this information may help us increase dose intensity to brain, head and neck tumors that have until now evaded treatment."
Successfully treating brain tumors is difficult because of the brain's natural defense, the blood-brain barrier. In the early 1980s, Neuwelt pioneered a unique method of temporarily opening this barrier, allowing chemotherapy to pass into the brain and reach the tumor. When compared to standard chemotherapy, the blood-brain barrier disruption procedure increases the delivery of the drugs to the tumor and its surrounding area by ten- to a hundredfold.
However, brain tumor patients treated with high-dose chemotherapy can suffer bone marrow toxicity, so the use of thiols, or sulfur-containing agents, was introduced to offset the harmful effects of chemotherapy.
In this new procedure, Neuwelt found that the simultaneous infusion of thiols into the left (or descending) aorta and chemotherapy agents into the arteries supplying the brain (i.e., the carotid and vertebral arteries) produced an effective and relatively safe therapy to protect the bone marrow without impairing the effectiveness of chemotherapy against tumor cells in the brain.
In his newly begun clinical trial, Neuwelt is using the procedure on brain tumor patients to help determine the most effective dosage of thiols to preserve marrow health while retaining chemotherapy effectiveness.
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