Robert A. Swanson, who co-founded Genentech and is considered a father of the biotechnology industry, was only 52 when he died in 1999, one year after a diagnosis of brain cancer.
In his own company’s laboratories was a new experimental drug that, it turns out, might have helped him. In recent studies, that drug, Avastin, seems to shrink tumors, although it is still not clear how much longer this may help patients live.
Avastin, already widely used to treat other types of cancer, is leading a pack of new drugs that look promising as treatments for brain cancer, one of the deadliest and least treatable forms of cancer. The disease has received public attention this week with news that Senator Edward M. Kennedy has a malignant glioma, the worst class of brain tumor.
While details of the 76-year-old senator’s cancer and his possible treatment are not yet known, glioma has a grim prognosis. Half of people with glioblastoma multiforme, the most common and deadliest of the gliomas, die within 15 months.
For decades, cancer drugs have been unable to make much of a change in those statistics. But now some experts hope that new drugs, some developed using new biotechnology techniques, can improve the outlook.
“I think that what you are going to see in the next five years is substantial improvement in survival,” said Dr. Henry S. Friedman, a brain cancer specialist at Duke University. “For the first time the pot seems to be boiling over with a number of different options, while 10 years ago we had nothing.”
Already, the brain cancer drug Temodar, a pill sold by Schering-Plough, is on track to surpass $1 billion in sales this year, which would make it the first blockbuster drug for brain cancer. And other treatments still in the experimental stage are showing hints of promise.
One is a cancer “vaccine,” which aims to train the patient’s immune system to attack the tumor. An advocate for it is Cameron Mitchell, a 51-year-old man who formerly ran a coin laundry business in Grand Rapids, Mich. One Saturday morning he collapsed at home, writhing in convulsions. It was the first signal of a brain cancer that his doctors said would probably kill him within a year and a half.
That was in March 2004. Four years later Mr. Mitchell is leading what he calls a fairly normal life, although he can no longer drive because of occasional seizures.
He credits his longevity to the experimental cancer vaccine that he has been taking once a month at Duke. Pfizer recently agreed to pay at least $50 million for rights to the treatment from the biotechnology company Avant Immunotherapeutics.
In early clinical trials, patients lived roughly 30 months on average, about twice what might be expected. Others being treated in a clinical trial include Bobby Murcer, the New York Yankees broadcaster and former player.
Many experts, to be sure, voice caution about the pace of progress against brain cancer. They point out that neither Avastin nor the vaccine has been shown to lengthen lives when compared with a placebo or another other drug in a clinical trial.
Drugs often look good in early testing because doctors, either consciously or subconsciously, choose to try them on the patients with the best prospects. Mr. Mitchell might have survived anyway.
“This is a very select population of patients,” said Dr. Jeffrey Raizer, director of the medical neuro-oncology program at Northwestern University. “There are two- to four-year survivors with these tumors who haven’t had the vaccine therapy.”
But virtually all experts agree there has been a sharp increase in the number of compounds being tested against brain cancer, in response to new scientific understanding of cancer and the changing economics of the pharmaceutical business.
For decades brain cancer was simply not an attractive area for drug makers.
Drugs rarely worked, in part because the blood-brain barrier, intended to shield the organ from certain chemicals in the blood, also blocked the drugs from reaching the tumors.
Moreover, the market was perceived to be small. There are only about 22,000 new cases of all brain and nervous system cancers in the United States each year, only a tenth as many as there are lung cancers, according to the American Cancer Society. The rapid death rate also limits the appeal of developing drugs.
“The typical life span isn’t that long, so it doesn’t have the recurring revenue stream, to put it bluntly,” said Stephen M. Case, chairman of Accelerate Brain Cancer Cure, a nonprofit group that spurs research on treatments for the disease. Mr. Case, a founder of America Online, started the group with his brother Daniel, the former chief of the investment bank Hambrecht & Quist, who died from brain cancer in 2002 at age 44.
But the situation is changing. As pharmaceutical companies have been able to sharply raise prices for cancer drugs in recent years, it has become possible for treatments for even rare cancers to have hefty sales — as demonstrated by Temodar.
New drugs are considered vital to the fight against brain cancer. Surgery and radiation therapy, which are also mainstays of treatment, might not improve much more. And they still can miss microscopic pockets of cancerous cells.
“We’ve reached our maximum limit that we can achieve with surgery,” said Dr. Keith Black, the chairman of neurosurgery at Cedars-Sinai Medical Center in Los Angeles.
Drugs, which can find those lurking cancerous cells by molecular means, might be the best option for further improvement.
Drug therapy made a big gain in 2004, when a trial showed that Temodar, combined with radiation, extended the median survival of patients in a clinical trial to 14.6 months, compared with 12.1 months for patients who received only radiation.
After four years, 12 percent of those who received Temodar, which is called Temodal outside the United States, were still alive, compared with only 3 percent of those in the control group.
Among drugs now in the pipeline, most attention is focused on Genentech’s Avastin. The company says it will file this year for federal approval of the drug to treat glioblastoma multiforme patients who have a relapse.
Avastin works by blocking the flow of blood that brings oxygen and nourishment to tumors. On brain scans, Avastin seems to shrink many tumors.
“This is a remarkable, miraculous response on the imaging that we’ve never seen before,” said Dr. Lawrence Recht, professor of neurology at Stanford University.
But there is a catch, he and others said. What the scans might be showing is that Avastin is reducing the swelling in the brain caused by leaking blood, not actually reducing the tumor size.
Even that can have a benefit because the swelling can cause neurological problems like those affecting speech or motion. In a clinical trial, patients who got Avastin alone had a median survival of more than nine months. Doctors said such patients might have been expected to live six months.
Other drugs that also work at least in part by blocking blood flow to the tumor are also in clinical trials. Most uncertain are the so-called cancer vaccines, which do not prevent disease like a measles vaccine. Rather they aim to treat the disease by harnessing the patient’s own immune system. No such therapeutic cancer vaccine has ever performed well enough to win approval in the United States.
Besides the Avant vaccine, another is being tested by Northwest Biotherapeutics. Eight of the first 16 treated patients have lived at least three years, said Dr. Linda M. Liau of the University of California, Los Angeles, who initially developed the treatment.
One of those patients, Kevin Carlberg, a 30-year-old Hollywood rock musician, has lived more than five years, getting married, having a daughter, running a marathon and recording new CDs.
“I guess I’m living proof that miracles do happen,” he said. But whether that miracle is because of the vaccine is still open to question.