Cancer Drugs Show Promise
'Targeted' Therapies Block Disease's Molecular Signals
By Rob Stein
Washington Post Staff Writer
Sunday, June 6, 2004; Page A18
A new, highly anticipated generation of cancer drugs has begun showing promise for treating an array of tumors that fail to respond to existing therapies, researchers reported yesterday.
A spate of new studies found the drugs can prolong the lives of patients suffering from advanced cancers of the lung, kidney and head and neck -- all notoriously difficult to treat, researchers said.
While still early, the findings are the latest signs that scientists have begun to translate decades of research into the fundamental biology of cancer into treatments that can help patients whose cancer is impervious to traditional therapies. The new drugs are known as "targeted" therapies because they pinpoint newly identified molecular signals that make cancer cells grow.
"We now have the ability to use these smart bombs, these laser-guided therapies, that go after something that causes the cancer cell to grow. That's extraordinary," said Roy Herbst of the University of Texas M.D. Anderson Cancer Center in Houston.
"We've been hearing about this for years, but this is different. We're finally seeing them work in patients," said Herbst at the American Society of Clinical Oncology's annual meeting in New Orleans, where the latest findings are being presented.
Although the results have been in patients with advanced cancer, scientists are optimistic the drugs will prove effective against the disease at earlier stages. At the same time, some researchers think that even if the drugs fail to cure cancer in many patients, they could keep them alive for years, or even decades, transforming cancer into more of a chronic disease similar to diabetes or heart disease. The findings also come as researchers are reporting some of the first success in tailoring cancer treatment to an individual's genetic makeup.
"It's just an incredible time. We're basically translating all the molecular biology and lab work from the last 10 or 20 years into treatments for patients. What was always a dream is now becoming a reality," Herbst said. "The whole paradigm is really shifting."
The most promising of the new studies released yesterday involved 731 patients whose lives were being measured in months. Standard chemotherapy had been useless against their non-small-cell lung cancer -- the most common form of lung cancer, which is the leading cancer killer.
Patients who received a new drug called Tarceva, which blocks a signal that makes cancer cells grow, lived about two months longer than those who received a placebo, with more than one-third surviving longer than a year, compared with only 20 percent of those getting the dummy drug, researchers reported.
"This is a landmark trial," said Frances Shepherd, a lung cancer researcher at the Princess Margaret Hospital in Toronto, who led the international study. "Even though the numbers of months seem small, for this group of patients, who are desperately sick and have virtually no options for treatment, this is highly significant. This is the first study of this class of agent to show a survival benefit."
Tarceva often causes a rash and diarrhea, but overall the patients taking the drug had a much better quality of life -- far less pain and coughing, the researchers found.
Tarceva also appeared to extend the lives of patients suffering from advanced kidney cancer when combined with another new drug, called Avastin, which cuts off blood supplies to tumors.
Of 62 patients who received the two-drug combination, 21 percent of the patients had their tumors shrink by at least half, another 21 percent had small shrinkages and 45 percent were stabilized, the researchers reported. About 81 percent survived for one year, whereas ordinarily about half of the patients would have been expected to die.
"This appears to be one of the most active regimens as well as one of the most well tolerated regimens that's been evaluated for advanced kidney cancer," said John D. Hainsworth of the Sarah Cannon Cancer Center in Nashville, who led the study. "This is the direction that a lot of investigational trials are going to go in -- combining these new targeted therapies."
Another experimental drug in the same class as Tarceva, called SU11248, also showed promise when tested on 63 patients with advanced kidney cancer. More than one-third of the patients saw their tumors shrink by at least half, and a quarter stabilized for more than four months, researchers reported. Similarly, another experimental drug, BAY 43-9006, produced encouraging results when tested in kidney cancer patients.
"This is the first ray of hope of promise in this cancer that I've seen since the 1980s," said Robert J. Motzer of the Memorial Sloan-Kettering Cancer Center in New York, who led the study. "Kidney cancer stands out as one of the most unyielding, difficult cancers to treat. When promising results are shown in one of the toughest cancers to treat, that's a real mark."
Another study found that the drug Erbitux, which is similar to Tarceva, appeared effective for treating advanced cases of head and neck cancer. In a study involving 424 patients, those who took Erbitux along with radiation were much less likely to have their tumors progress and were significantly more likely to survive than those who only received radiation, according to James A. Bonner of the University of Alabama at Birmingham, who led the study.
"These drugs are really demonstrating an effect in patients," Herbst said. "And not just one drug, but a whole series of them."
Meanwhile, two other studies found that early stage lung cancer patients were much more likely to survive if they received standard chemotherapy after undergoing surgery -- findings that some experts said would transform the treatment of the common malignancy.
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