Gene test offers hope for brain cancer patients

/ Source: The Associated Press

A simple genetic test can identify which patients with deadly brain tumors will be helped by a treatment hailed as the first significant advance against the disease in decades, scientists said Wednesday.

A study by Swiss doctors, presented Wednesday at a conference in Geneva, found 46 percent of patients with the right genetic profile were alive after two years if they got the drug, temozolomide, as well as radiotherapy. The chance of survival among patients with the wrong genetic signature was only 14 percent — not much better than with radiotherapy alone.

Experts say the test could avoid raising false hopes in those patients with the deadly tumors, known as glioblastomas, who would get no benefit, freeing doctors to try other approaches. The finding is another step in the quest for individual tailoring of cancer treatment, they say.

“The problem we’ve had with temozolomide is that if it’s not working, then you’re left to watch the disease progress,” said Dr. Ralph Vance, national president of the American Cancer Society, who was not involved with the research.

“This is a wonderful thing if we could test the glioblastoma, then we won’t be guessing and wasting time for people in whom this won’t work because ... we could get them in another trial that would at least give them a chance,” said Vance, a professor of medicine at the University of Mississippi.

Only some patients respond to drug
Radiation and surgery have been the first-line treatments for glioblastomas, but even with them, the disease usually kills within a year or less. Intravenous chemotherapy available since the 1970s improves these odds only marginally and can have serious side effects.

Unlike most cancer, which kills by spreading through the body, glioblastomas grow quickly inside the head, destroying everything in their path. They are the most aggressive of the 100 or so forms of cancer that originate in the brain and account for half or more of all cases. Around the world, 175,000 cases are diagnosed annually, killing 125,000 people.

Earlier this year, the Swiss scientists reported that giving temozolomide to patients early in treatment could prolong the lives of some people. About 26 percent of the patients that got the drug were alive after two years.

However, they could not tell which patients the drug worked for or whether the results would look even better if the drug was given just to those who responded to it.

In the experiment reported Wednesday, the researchers, led by Dr. Monika Hegi, head of the tumor biology and genetics lab at University Hospital in Lausanne, Switzerland, examined the genetic makeup of 106 people given the drug in the earlier study.

Key gene involved in DNA repair
They found the key to predicting which patients would benefit from the drug was a gene involved in DNA repair and its status in the patient’s tumor. If the gene was switched off, the drug worked, but if the gene was active, the drug had little effect.

“These results are important because temozolomide is a drug that acts directly against DNA to slow down the replication of cancer cells. So it is bad news if the patient has (active gene) status because the DNA in these rogue cancer cells is being repaired as fast as the drug causes damage. This means the cancer cells are able to survive the drug’s onslaught,” said Hegi.

In patients with the silent gene, the chance of being alive after two years was 46 percent. Only 14 percent of those with the active gene survived the two years.

It is too early to say whether the drug will cure some patients, Hegi said, but temozolomide is the latest drug to be added to an arsenal of medicines only given to people with a certain genetic profile that doctors know will respond well.

Other targeted drugs include the breast cancer treatment Herceptin, which is given only to women whose key gene is overactive, and Iressa, a drug scientists have found seems to work only in lung cancer that has mutated in a certain way.