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Osmotic Opening of Blood-Brain Barrier Improves Chemotherapy Outcome in Brain Tumour Patients: Presented at ICACT
By Adrian Burton
Special to DG News
PARIS, FRANCE -- February 3, 2003 -- Opening up the blood-brain barrier with mannitol significantly improves survival rates in patients undergoing chemotherapy for oligodendroglioma, oligoastrocytoma or aggressive oligodendroglioma.
Dr. Edward Neuwelt, professor of medicine at Oregon Health Sciences University, Portland, Oregon, reported the results here February 2nd at the 14th International Congress on Anti-Cancer Treatment.
"The idea is that by making the blood-brain barrier permeable for 15 to 30 minutes, with an intra-arterial injection of 25% mannitol we can increase delivery of chemotherapy agents to the [central nervous system] by about 100-fold even though we use normal systemic [chemotherapy] doses."
Dr. Neuwelt explained that as well as increasing dose delivery to the central nervous system (CNS), circulating chemotherapeutic agents can be neutralised after the 15-30 blood-brain barrier permeability window closes by injecting chemoprotectors such as sodium thiosulphate, therefore reducing toxicity to systemic tissues.
The researchers studied 23 men and 17 women with a median age of 43 years who had oligodendroglioma, oligoastrocytoma or aggressive oligodendroglioma -- three types of tumours that are known to be chemoresponsive.
Thirty-four patients received 1-250 mL of 25% mannitol, depending on blood flow, to open the blood-brain barrier before receiving chemotherapy with a combination of carboplatin 400 mg/m2, etoposide 400 mg/m2 and cytoxin 660mg/m2 once a month for 12 months or until loss of response. Six received chemotherapy alone. Chemotherapy neutralisers were given 30 minutes after mannitol administration.
Of the 39 evaluable patients, complete responses were seen in 2 patients, partial responses were seen in 9, stable disease in 27, and 1 patient's disease progressed.
The overall median time from study entry to progression was 346 days, and median survival time was 572 days.
Significant differences were found when the researchers compared the results of the 34 patients who received mannitol with those of the six who had not. Median survival of those who received mannitol was 849 days compared to 178 in the standard chemotherapy group (p<0.0001).
"The [question] is, can we do dose intensive chemotherapy without systemic toxicity?" said Dr. Neuwelt. "Until now the problem has been how to get the drugs into the CNS 'sanctuary' in dose-intensive regimens without causing that toxicity. But this system looks like it will do the job."
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