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updated 6/25/2004 12:23:39 PM ET 2004-06-25T16:23:39

One of the most frustrating aspects of cancer treatment is not knowing why particular drug therapies help some patients yet fail to work in, or even significantly harm, others.

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Many times, it’s a crapshoot. Lucky patients will respond well while the unlucky ones may lose precious time taking a drug that will never work, or they could suffer unusually severe, occasionally fatal reactions, as sometimes happens with standard chemotherapy.

But researchers involved in the new field of individualized cancer care are seeking ways to stack the odds in each patient's favor. And encouraged by recent reports, a growing number of doctors envision a day when cancer care is commonly personalized to a particular patient's genetic make-up.

'Holy Grail' of cancer treatment
“The Holy Grail for a lot of people in oncology is that we will individualize our treatment for every patient,” says Dr. John T. Cole, head of oncology at the Ochsner Clinic Foundation in New Orleans.

“They’ll be given a combination of standard and targeted treatments with maximum benefit and minimal toxicity,” he says.

Doctors like Cole hope that cancer patients will eventually undergo routine blood tests or tissue biopsies to identify genetic markers that offer clues about which treatments will work and who’s most likely to experience the greatest side effects or a cancer recurrence.

“Based on my crystal ball, I think this is going to be very important,” says Dr. David Johnson, president of the American Society of Clinical Oncology (ASCO) and director of oncology at Vanderbilt University in Nashville, Tenn.

Targeting the targeted therapies
Some research is already yielding results that could soon help patients.

Just this spring, two teams of doctors in Boston announced they had found that lung cancer patients with specific genetic mutations in their tumors were highly likely to respond to the new drug Iressa, while those without the mutations weren’t. The finding explains why the drug, which targets the cancer-fueling epidermal growth factor receptor (EGFR), only works in about 10 percent of these patients — just those with abnormal EGFR genes.

OVER SIX MILLION IRESSA DISTRIBUTED
Jonathan Kirn  /  FPS file
AstraZeneca's David Barrow displays an Iressa pill over a batch of bottles waiting to be filled at the AstraZeneca facility in Newark, Del. Puzzled by why the drug only works in 10 percent of lung cancer patients, doctors recently found that these people's tumors harbor specific gene mutations.
The discovery, which could help doctors determine whether to try Iressa versus another therapy, is “an illustration of the power of this type of approach to treating patients,” says Johnson.

While there's much excitement about targeted therapies like Iressa — because unlike chemotherapy and radiation they home in on cancer cells and spare healthy tissue — these drugs don't work well for everybody. But with a better understanding of precisely how the drugs function, doctors may gain the ability to “target the targeted therapies,” says Johnson.

“That’s the ultimate in personalized medicine,” he says.

Personalized medicine could also make good use of standard cancer treatments like chemotherapy, doctors say. Just as some people get too much chemotherapy, causing severe side effects, others may not get enough to properly fight their cancer.

"The future may be dosing drugs based on how people metabolize them," says Dr. George McDonald, head of gastroenterology and hepatology at the Fred Hutchinson Cancer Research Center in Seattle.

In his research, McDonald has found that blood samples can help predict which patients undergoing hematopoietic stem cell transplants for leukemia will experience liver damage from chemotherapy, based on how fast they metabolize an initial dose of the drug. His team is currently searching for genetic markers that determine how the drug is processed.

At ASCO’s annual meeting earlier this month in New Orleans, researchers reported several other findings in this field. Among them:

  • Colon cancer patients with certain genetic mutations were at increased risk for experiencing fatigue and distress when undergoing chemotherapy, according to one report. "We believe we've found evidence of a relationship between genetic make-up of patients and their quality of life," says study author Jeff Sloan of the Mayo Clinic in Rochester, Minn.

  • In breast cancer patients, one study found that the expression of certain gene patterns in tumors could predict which women with early-stage disease would respond to tamoxifen given after their surgery to prevent disease recurrence. And in postmenopausal women with advanced disease, researchers reported that gene alterations could predict how well a patient would respond to the drug Femara.

  • A study of patients with advanced lung cancer found that those with a certain gene variation were twice as likely as those with a normal copy of the gene to suffer severe gastrointestinal side effects from their radiation treatments and chemotherapy. And in another study suggesting that ethnicity plays a role in cancer care, researchers found that Japanese patients undergoing chemo for lung cancer survived longer but had more side effects than U.S. patients.

Research picking up speed
As the field -- which doctors call pharmacogenomics -- grows and research picks up speed, doctors hope patients will regularly benefit sometime in the near future.

“It’s a field that has really taken off over the last few years,” Cole says.

He predicts that within the next five years, individualized cancer care will be routine for many patients.

The technology to test patients’ genes is widely available, Johnson notes, but just how soon it will be applied to personalized cancer care depends on how fast the discoveries come and can be validated with additional research.

“I’m optimistic that it’s going to happen soon,” he says.

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