PREPARATION Dennis Sugrue, of Stamford, Conn., had staples removed before undergoing a procedure in which the cancer drug Avastin was injected into his brain.
It was approved for intravenous use — to be dripped into a vein, usually in the arm — but he said Mr. Sugrue would be an ideal candidate for his study, in which the drug would be infused directly into an artery in the brain, producing levels at least 50 times what the intravenous route could achieve. One other patient had been treated that way, and M.R.I. scans showed that recurring tumors seemed to have melted away.
Mr. Sugrue said he was all for it, even though Dr. Boockvar warned him that the drug was no magic bullet. Then Dr. Boockvar ticked off the risks from a second brain operation.
“I have to quote you a 5 percent risk you’ll be visibly weak,” he said. “A 1 percent chance of paralysis on the left side.”
Mr. Sugrue wiped his eyes and began to apologize for losing his composure, but the surgeon cut him off and said, “In neurosurgery they say that if you don’t make your patient cry, you haven’t gotten informed consent.”
The trial grew out of a conversation about a year ago between Dr. Boockvar and Dr. Riina, an expert in using microcatheters to treat strokes.
“I said, ‘Why can’t you infuse chemotherapy for my brain tumor patients?’ ” Dr. Boockvar recalled. “And he said: ‘I can. Just show me what you want to do.’ ”
Dr. Riina said, “Technically, I can go anywhere in your brain.”
He said microcatheter technology had advanced “light-years” in the last decade and was just waiting for a new drug to come along for glioblastoma.
They wrote up a plan to test what they called “superselective intra-arterial cerebral infusion” of Avastin in 30 patients with glioblastomas that had recurred after standard treatment. Each patient would receive just one treatment directed into the brain, followed weeks later by a series of intravenous treatments with Avastin.
Their study involves a technique first developed about 30 years ago, which uses mannitol to open the blood-brain barrier temporarily to get chemotherapy into the brain. Mannitol pulls water out of the tightly packed cells lining the capillaries so that they shrink and pull away from one another, opening up gaps through which drug molecules can pass into the brain.
The technique was developed by Dr. Edward A. Neuwelt, a neurosurgeon at Oregon Health Sciences University and the Veterans Affairs Hospital in Portland. Its best results have been in people with a rare type of brain tumor called a primary central nervous system lymphoma. But it has not been helpful with glioblastoma, because until recently there was no chemotherapy to infuse that would have much effect on those tumors.
Dr. Neuwelt said that Avastin had helped to renew interest in opening the blood-brain barrier but that researchers disagreed about whether the drug would lend itself to that use.
Avastin starves tumors by blocking the growth of new blood vessels, which they need to survive. Dr. Boockvar said microcatheters should increase the odds of success by delivering a high dose of the drug directly to where it was needed most. Earlier research with other drugs used larger catheters inserted into the carotid arteries, which feed the entire brain — meaning that the tumor did not receive the most concentrated dose and that healthy brain tissue was exposed to the toxic drugs.
By mid-November, the researchers had treated five patients, including Mr. Sugrue; they first infused mannitol, waited five minutes and then sprayed in the Avastin. In all the patients’ M.R.I. scans, the telltale bright spots that marked tumor growth faded away after the treatment.
“I can’t tell you what it means,” Dr. Boockvar said. “Nobody knows.”
Indeed, the death of the first patient was a reminder that glioblastoma can invade other parts of the brain and the spinal fluid and that the highly localized spray of Avastin might miss deadly seeds of cancer.
But Dr. Boockvar remained hopeful for the remaining patients, describing the scans as “astronomically far better than I had anticipated.”
Hope and Anxiety
Mr. Sugrue was still in the hospital in late September when Dr. Boockvar burst into his room and got him out of bed to look at his own before-and-after scans.
“He took me to this room with all these computers and said, ‘I’ve got to show you this,’ ” Mr. Sugrue recalled. “This M.R.I. was a thing of beauty. I’m excited that he’s excited. That means a lot to me.”
Dr. Boockvar said: “Avastin may not be the best drug for this delivery technique. What’s exciting about our results is that we’ve proven there is a local effect.
“Suppose someone said, ‘I have much better drug.’ Now I can say I at least have a delivery system.”
With patients, Dr. Boockvar tries to walk a fine line, trying to level with them and yet not rob them of all hope. He knows the emotional toll that a cancer diagnosis can take: his own father had leukemia for about eight years and died in September. Mrs. Sugrue said the doctor urged her and her husband to resist doing an Internet search for glioblastoma because they would just read that it was a death sentence.
They said they tried to follow his advice, but when the subject of prognosis came up in an interview, both had tears in their eyes.
“You don’t ask the question if you don’t want the answer,” Mrs. Sugrue said. “What will be, will be. You do what you can.” ( nytimes.com )
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