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Old 03-02-2007, 12:06 PM   #1
Lani
Senior Member
 
Join Date: Mar 2006
Posts: 4,778
for those with (or worried about) brain mets Avastin seems to cross the bbb

Blood brain barrier) and is effective in prolonging survival and function when combined with chemo in primary brain tumor (glioma). The fact that it crosses the blood brain barrier in these tumors (hope same will be the case for breast ca brain mets) and has been shown to be syngergistic with herceptin in a relatively small group of metastatic breast patients studied by Dr. Mark Pegram, is reason to hope (especially as it is already FDA approved for other purposes):

Cancer Drug Can Extend Survival in Patients with Deadly Brain Tumors [DukeMedNews]
DURHAM, N.C. — Avastin, a relatively new type of drug that shrinks cancerous tumors by cutting off their blood supply, can slow the growth of the most common and deadly form of brain cancer, a pilot study conducted at Duke University Medical Center has found.

The study marks the first time that Avastin has been tested against brain tumors, the researchers said. The drug, whose chemical name is bevacizumab, currently is used to treat lung and colorectal cancers.

The researchers tested the effectiveness of Avastin in conjunction with a standard chemotherapy agent in patients with recurrent cancerous brain tumors called gliomas. They found that the two drugs together halted tumor growth up to twice as long as comparative therapies. Though gliomas remain incurable in nearly all cases, the combined drug therapy may buy precious time and preserve physical and mental function longer for patients facing this grim diagnosis, the researchers said.

"These results are exciting because of the possible implications for a patient population that currently has the poorest possible prognosis going into treatment, those with malignant brain tumors that have recurred after initial treatment," said James Vredenburgh, M.D., a brain cancer specialist at Duke's Preston Robert Tisch Brain Tumor Center and lead researcher on the study.

The findings will appear in the Feb. 20, 2007, issue of the journal Clinical Cancer Research. The study was funded by the National Institutes of Health, the Preston Robert Tisch Brain Tumor Research Fund, the Bryan Cless Research Fund and Genentech, the maker of Avastin.



ABSTRACT: Phase II Trial of Bevacizumab and Irinotecan in Recurrent Malignant Glioma [Clinical Cancer Research]
Purpose: Recurrent grade III-IV gliomas have a dismal prognosis with minimal improvements in survival seen following currently available salvage therapy. This study was conducted to determine if the combination of a novel antiangiogenic therapy, bevacizumab, and a cytotoxic agent, irinotecan, is safe and effective for patients with recurrent grade III-IV glioma.

Experimental Design: We conducted a phase II trial of bevacizumab and irinotecan in adults with recurrent grade III-IV glioma. Patients with evidence of intracranial hemorrhage on initial brain magnetic resonance imaging were excluded. Patients were scheduled to receive bevacizumab and irinotecan i.v. every 2 weeks of a 6-week cycle. Bevacizumab was administered at 10 mg/kg. The dose of irinotecan was determined based on antiepileptic use: patients taking enzyme-inducing antiepileptic drugs received 340 mg/m2, whereas patients not taking enzyme-inducing antiepileptic drugs received 125 mg/m2. Toxicity and response were assessed.

Results: Thirty-two patients were assessed (23 with grade IV glioma and 9 with grade III glioma). Radiographic responses were noted in 63% (20 of 32) of patients (14 of 23 grade IV patients and 6 of 9 grade III patients). The median progression-free survival was 23 weeks for all patients (95% confidence interval, 15-30 weeks; 20 weeks for grade IV patients and 30 weeks for grade III patients). The 6-month progression-free survival probability was 38% and the 6-month overall survival probability was 72%. No central nervous system hemorrhages occurred, but three patients developed deep venous thromboses or pulmonary emboli, and one patient had an arterial ischemic stroke.

Conclusions: The combination of bevacizumab and irinotecan is an active regimen for recurrent grade III-IV glioma with acceptable toxicity.
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