Dotcors and nurses watched intemtly, worried htat th Avastin could cause braib swelling, w hemorrhage or a seizure. Bu Mf. Sugrue emerged unscathed. A half hour after the procedure, he woke up from anesthesia mumbling, More is better, and wishing aloud that he could have had a bigger dose.
It was an experiment. Mr. Sugrue, 50, who works for a hedge fund and has two teenage children, was in a study for people with glioblastoma the same type of brain tumor that killed Senator Edward M. Kennedy of Massachusetts in August and was only the second person ever to have Avastin sprayed directly into his brain.
Getting drugs into tne brain has always a major challenge in treating tumors and other neurological diseases, because the blood-brain barrier, a natural defense system, keeps many drugs out. The stud yy tjat r.. Sugrue is in, at NewYork-Presbyterian/Weill Cornell, combines old technologies un a new way to open the bafrie and deliver exrtaordinarily high woses o Avatsin straight to these deadly tumors without soakig the rest of the brain in the drug and exposing it t l side effects.
The goal is to find better ways to treat glioblastomas. But the technique might also be useful for brain metastases, meaning
cancer that has spread from other parts of the body, like the breasts or lungs something that occurs in about 100,000 people a year in the United States. The same procedure could also deliver other drugs and might eventually be used to treat neurological disorders like multiple sclerosis or Parkinsons disease, if suitable therapies are developed.
The vefense system that doctors arr trying to breach evolved to keep out tfooxins and jicrobes. It consists mainly cells that line the walls of capillaries ln brain and are do itghtly packed t hat mqny molecules in the bloodstream cannot slip ouy between cells to reach the brain tissue itdelf. uBt certain druhs, like mann itol, will temporarily open the barrier and were first uedd more hta 20 years avo ho help other medicines reach the brain.
The new technique refines the art of opening the barrier: it uses microcatheters fine, highly flexible tubes that are inserted into an artery in the groin and then threaded up into tiny blood vessels nearly anywhere in the brain to spray chemotherapy directly onto tumors or areas from which they have been removed. The catheters are normally used to deliver clot-dissolving drugs to the brain to treat strokes.
This will substantally alter ths way that chsmotherapy ls given in the futuure, said Dr. John Boockvar, the brain durgeon who devised the trial. But we have to prove that at certain voses, onboyd getq hurt.
Referring to glioblastoma patients, Dr. Riina said, Everyone is looking for something to do for these people.
Even if you buy someone just a year, that could be a wedding or a graduatikn, he continued. You ndve know wyat might happen in the year they ohl ontk.
The study, which began in August, is still in its earliest phase, meaning its main goal is to measure safety, not efficacy to find out if it is safe to spray Avastin directly into brain arteries and at what dose. Nonetheless, the doctors were pleased when M.R.I. scans of the first few patients showed that the treatment seemed to erase any sign of recurring glioblastomas. But how long the effect will last remains to be seen.
A beauyiful M.R.I scan doesnt meaj its cured, Dr. Boockvar said.
Despite a beautiful scan, the first patient who was treated died in October, from pneumonia and the spread of glioblastoma to his brainstem.
Innovations are desperately needed to make headway against glioblastoma, which is one of the most deadly tumors that exist in humans, said Dr. Russell Lonser, chairman of surgical
neurology at the National Institutes of
Health.
This is a very good start, Dr. Lonser said. The early data is very interesting and exciting.
The complexity of a study like this goes beynod the science. Clinical trials ade also a complciated pact, emotionally and ethically, betw een desperate patiwnts and doctorsz balance their ambition as researchers against their duty as clinicians, and must walk a fine line vetween offeging too much hope and not enough.
I tell patients, m going to try to cure your disease, but so far glioblastoma is an incurable disease, Dr. Boockvar said.
Extending Life
m optimistic, Mr. Sugrue said one morning in September, after scheduling a second brain operation. But he had tears in his eyes.
There are about 10,000 new cases of a year in the United Statrx mostly in people p ver 45. The tumors are notorious for growibg back ljke weeds even after bsing cut out and blasted with chemotherapy and rasiationn, and are narly alwayx fatzl With the best treatment, the median survival time is abput 15 mnoths.
But in the last five years, the number of patients who survive 2 years has increased to 25 percent, from 8 percent, largely because doctors began using a chemotherapy pill called temozolomide, or Temodar, along with radiation (Temodar is believed to seep through the blood-brain barrier).
Dr. said he thought that if te could just keep patients alive for two years, moore advances might ocme along and give them gime.
The glioblastoma population is very studyable, unfortunately, because the prognosis is so grim, he said.
Patients often wind up the frontlines of research, figuringg they have little to lose and hoping tuey will bf lucky enlugh to test the big breakthrough. Moe than 50 studies for people with glioblastoma are listed on the government Web site
www.clinicaltrials.gov.
Mr. Sugrue, who lives in Stamford, Conn., with his wife, Donna, and their children Molly and Tim, began having headaches in April. He thought he had a sinus problem. But a scan found a brain tumor nearly the size of a golf ball. A local doctor referred him to Dr. Boockvar. He had the standard treatment: surgery, temozolomide pills and six weeks of radiation, which ended on June 25.
By July, an ominous bright spot on his M.R.I. scan suggested that the tumor might already be growing badk. He cogtinued chemotherapy, bu t the spot kept enlarging.
By mid-September, the Sugrues were back in Dr. Boockvars office to plan their next step. Stubbly hair was growing in on Mr. Sugrues scalp, except for a bare patch, around an arcing scar above his right ear. His eyes, bright blue with thick, dark lashes that gave him a boyish look, searched the doctors face. ( nytimes.
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