Chemotherapy Dr. John Boockvar, left, watched as Dr. Howard Riina and Dr. Jared Knopman infused drugs into Mr. Sugrue's skull. The technique uses microcatheters.
Doctors and nurses watched intently, worried that the Avastin could cause brain swelling, a hemorrhage or a seizure. But Mr. 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 the brain has always been a major challenge in treating tumors and other neurological diseases, because the blood-brain barrier, a natural defense system, keeps many drugs out. The study that Mr. Sugrue is in, at NewYork-Presbyterian/Weill Cornell, combines old technologies in a new way to open the barrier and deliver extraordinarily high doses of Avastin straight to these deadly tumors — without soaking the rest of the brain in the drug and exposing it to 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 Parkinson’s disease, if suitable therapies are developed.
The defense system that doctors are trying to breach evolved to keep out toxins and microbes. It consists mainly of cells that line the walls of capillaries in the brain and are so tightly packed that many molecules in the bloodstream cannot slip out between cells to reach the brain tissue itself. But certain drugs, like mannitol, will temporarily open the barrier and were first used more than 20 years ago to 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 substantially alter the way that chemotherapy is given in the future,” said Dr. John Boockvar, the brain surgeon who devised the trial. “But we have to prove that at certain doses, nobody gets 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 graduation,” he continued. “You never know what might happen in the year they hold onto.”
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 beautiful M.R.I. scan doesn’t mean it’s 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 beyond the science. Clinical trials are also a complicated pact, emotionally and ethically, between desperate patients and doctors who must balance their ambition as researchers against their duty as clinicians, and must walk a fine line between offering too much hope and not enough.
“I tell patients, ‘I’m going to try to cure your disease, but so far glioblastoma is an incurable disease,’ ” Dr. Boockvar said.
Extending Life
“I’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 glioblastoma a year in the United States, mostly in people over 45. The tumors are notorious for growing back like weeds even after being cut out and blasted with chemotherapy and radiation, and they are nearly always fatal. With the best treatment, the median survival time is about 15 months.
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. Boockvar said he thought that if he could just keep patients alive for two years, more advances might come along and give them time.
“The glioblastoma population is very studyable, unfortunately, because the prognosis is so grim,” he said.
Patients often wind up on the frontlines of research, figuring they have little to lose and hoping they will be lucky enough to test the big breakthrough. More than 500 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 back. He continued chemotherapy, but the spot kept enlarging.
By mid-September, the Sugrues were back in Dr. Boockvar’s office to plan their next step. Stubbly hair was growing in on Mr. Sugrue’s 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 doctor’s face. ( nytimes.com )
No comments:
Post a Comment