Thursday, November 19, 2009

another good article on intra-arterial Avastin delivery

Dad did some research and found a great article from about the experimental work mentioned in the New York Times the other day. Excerpts:

Neurosurgeons from New York-Presbyterian Hospital/Weill Cornell Medical Center performed the world's first intra-arterial cerebral infusion of Avastin (bevacizumab) directly into a patient's malignant brain tumor. This novel intra-arterial (IA) technique may expose the cancer to higher doses of the drug therapy, while possibly sparing the patient common side effects of receiving the drug intravenously (IV) or throughout their body.

The investigative procedure — called super selective intra-arterial cerebral infusion of Avastin — has been successfully performed on five patients with promising results. Details of the first case are scheduled for publication in the next issue of Journal of Experimental Therapeutics and Oncology.

The researchers are currently enrolling patients for the Phase I study, which will test the safety and tolerability of this new method of drug delivery. If proven successful, New York-Presbyterian/Weill Cornell physician-scientists believe that this promising method may one day offer patients a new and better therapy for glioblastoma multiforme (GBM), a common type of brain cancer that has not responded well to currently available therapies. In addition, the authors believe that this technique may herald the birth of a new field of "interventional neuro-oncology."

"We believe that infusing Avastin directly via the cerebral arteries deep into the site of the brain tumor may help to kill off the cancer cells hiding within the tumor and adjacent brain tissue," explains co-author and study co-principal investigator (PI) Dr. John A. Boockvar, associate professor of neurological surgery at Weill Cornell Medical College and director of the brain tumor research laboratory at New York-Presbyterian Hospital/Weill Cornell Medical Center.

"We are combining the latest in drug treatment with a revolutionary delivery technique, which could potentially be more effective than currently available treatments," says co-author and co-PI, Dr. Howard Riina, co-director of interventional neuroradiology at New York-Presbyterian Hospital/Weill Cornell Medical Center and associate professor of neurological surgery, neurology and radiology at Weill Cornell Medical College.

Because of the blood-brain barrier (BBB), which prevents many IV-administered drugs from penetrating the blood vessel walls sufficiently in order to get into the brain, no one knows for sure if current drugs actually get into the brain after IV infusion.

"This new technique may be a way to get through that barrier and deliver higher doses of drug to the tumor with less toxicity to the patient," says Dr. Boockvar.

To deliver the drug, neurosurgeons direct a hair-thin microcatheter through blood vessels in the body, via the carotid artery running up the neck, and then into the smaller arteries deep in the brain. Upon arriving at the tumor site, a drug to open the blood-brain barrier is injected. After the BBB is temporarily opened — a window of time lasting approximately five minutes — the chemotherapeutic agent Avastin is injected directly into the malignant tumor.

Participants in the trial will be given varying doses of the drug in order to test which dose is best tolerated. Following this Phase I trial, the researchers plan to immediately begin a Phase II trial to test the technique's efficacy.


The current standard of care is to give patients with GBM the drug bevacizumab (Avastin) intravenously (IV) — delivering the drug directly into a vein. The drug works by slowing the growth of new blood vessels within tumors, cutting off the life-giving blood and then causing the cancer cells to die. In May 2009, the FDA approved Avastin for the treatment of GBM.

Study researchers are currently recruiting males or females, 18 years of age or older, with documented diagnosis of relapsed GBM, anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma (AOA) — two other types of brain tumors. The authors have no financial disclosures related to the study.

Whether Mom's tumors count as "relapsed" is open to question: if I understand "relapse" correctly, the tumors have to go away first before a relapse can be said to occur. Then again, maybe the appearance of a second and third tumor, despite ongoing therapy, is enough to qualify as a relapse. We'll have to find out whether Mom is even a candidate for this sort of research. I imagine she is, but we need to make sure.

Is a trip to New York in order? Dad's planning to call the medical center tomorrow. We need to start planning now, even if it turns out that we won't go. Timing is important here: Mom's current eight-week carboplatin regimen won't end until late December or early January; we won't be taking her to New York before that time, but if we do decide to enroll Mom in this trial, we plan to be on the road as soon as the carboplatin regimen is done.



Charles said...

Sorry for the retarded question here, but is this still a palliative treatment?

Kevin Kim said...

On the contrary, it's a good question. Historically, GBM tumors treated with Avastin become Avastin-resistant, so even with the new delivery system, I don't think we can view Avastin as a cure. It remains palliative in the sense that, by shrinking whatever tumors are hit with the drug, this relieves pressure on the surrounding brain tissue, improving cognitive function, reducing the incidence of seizures, etc. But in the end, the nature of GBM is to return in force, no matter the treatment, so even this new therapy is likely to be needed over and over again until the end.

The docs have all painted the same picture: prognosis for GBM patients of Mom's age is inevitably grim, but science continues to make incremental progress in the treatment of the disease. This new technique may, if proven safe, push the boundaries of life expectancy out even further.

I'm curious to know when Phase II trials are supposed to begin. While I'd seriously consider signing Mom up for Phase I, I'd much rather get her into Phase II.

Charles said...

Thanks for the info. I know so little that it's hard to know what is a good question and what isn't.

Kevin Kim said...

We're in the same boat you are, flailing in the dark, and learning as we go.