Newer anti-cancer drugs target specific cells with fewer side effects
By Deborah L. Shelton
http://www.JewishWorldReview.com | (MCT) When Glen Farkas was diagnosed with late-stage colorectal cancer in 2003, his chance of surviving five years was almost nil.
Trying to beat the odds, he chose to undergo radiation, surgery and painful five-hour-long infusions of a cocktail of chemotherapy drugs. The treatments held the cancer at bay for about a year, but the cancer returned with a vengeance, invading his liver, bone and lungs.
The second time around, a drug called Avastin was added to his chemotherapy regimen. Not widely available in 2003, Avastin required only 10 minutes to transfuse, was painless and didn't cause side effects, Farkas said. As an added plus, he got his chemo in pill form, instead of intravenously.
The Los Angeles ophthalmologist has been cancer-free since December 2006. "In my opinion, (the addition of Avastin) turned my case around and saved my life," Farkas said.
Today's anti-cancer drugs are a far cry from medicine's first chemotherapy - a form of mustard gas - developed at the University of Chicago and two other universities and approved 60 years ago last month by the U.S. Food and Drug Administration.
Thanks in part to advances in genetic science, chemo is becoming more effective and far less grueling, and is transforming treatment for many cancer patients. The array of cancer-fighting medications is growing, and they are aided by new drugs that help treat nausea, minimize pain and boost levels of white cells to fight infection.
More than half of all people diagnosed with cancer are prescribed chemotherapy, a general term for drugs used to stop cancer cells from growing. Its advantage over surgery and radiation is that drugs can wage war on cancer cells wherever they are in the body.
Older chemotherapy drugs caused many difficult side effects because they couldn't distinguish between healthy and cancerous cells and attacked other fast-growing cells in the body, including hair and blood cells. The newer drugs are tailored to specific types of cancer and target particular types of cancer cells.
"These drugs are certainly less toxic and more effective than they used to be, in some cases, dramatically more effective," said Dr. Thomas J. Smith, professor of medicine and palliative care at Virginia Commonwealth University Massey Cancer Center. "A handful of cancers are controllable now that weren't controllable five or 10 years ago."
The drug added to Farkas' regimen, Avastin, is an example of this relatively new type of "targeted" cancer therapy. It includes monoclonal antibodies, laboratory-produced molecules that are engineered to attach to specific defects in cancer cells. The antibody makes the cancer cell more visible to the immune system, blocks chemicals that signal the cell to grow, delivers radiation to cancer cells and allows anti-cancer drugs to penetrate into the cells.
Avastin is also an anti-angiogenesis drug, meaning it interferes with the vessels delivering blood to cancer cells. Without a plentiful blood supply, tumors can't grow.
Despite the advances, chemotherapy is still far from perfect, and the risk of debilitating side effects remains. Some people tolerate the drugs better than others, and some cancers respond better than others.
Suzanne Lindley, who lives in Texas, has experienced a range of side effects from chemo, from rashes to loss of feeling in her extremities.
"I think there's still a big communication gap between patients and physicians about how those side effects affect the person," said Lindley, diagnosed with advanced colon cancer that has since spread. "It's one thing to see the side effects on paper. We have to live with them. It's a matter of quality of life."
As the field advances and cancer treatment becomes more complex, experts say doctors and patients will have to communicate better about the best course of action. That's especially true for patients whose conditions are terminal and who do not want medical intervention that might do more harm than good to their quality of life.
Physicians are coming around to the idea that chemo should not be the default position, Smith said.
"It's very hard to sit across from someone and tell them that medical science does not have a way to make them live longer," Smith said. "It's a lot easier to just give another round of chemotherapy. But that has to change - and it is."
Increasingly, however, genetic tests are making it possible to tailor care so patients with treatable cancer receive drugs that are most likely to help them while avoiding the side effects of drugs that won't.
"It used to be, we gave everybody the same dose of chemotherapy and watched what happened and then made adjustments as necessary," said Dr. Richard Schilsky, a University of Chicago Medical Center oncologist who is president of the American Society of Clinical Oncology.
"We are now moving into an era where we can test people, for at least some of the chemotherapy drugs, to see if they will be able to tolerate the standard dose or not, so we can begin to make dose adjustments right from the start," he said.
For example, cancer specialists now agree that patients with advanced colon cancer should get a particular genetic test before taking two of the leading treatments. Oncologists adopted the change in February after studies found that two pricey drugs, Erbitux and Vectibix, were ineffective in 40 percent of patients.
One breakthrough in targeted cancer therapy was the development of the drug Gleevec, which works by turning off specific proteins in cancer cells that cause the cells to grow and multiply. It targets a cancer protein that causes a type of chronic myeloid leukemia, and another cancer protein, called Kit, that is the suspected cause of gastrointestinal stromal tumors.
"Gleevec is an example of a drug that hits a target and is well-tolerated," said Dr. Maurie Markman, vice president of clinical research at the University of Texas' MD Anderson Cancer Center. Over the next 10 to 20 years, he said, we will see many more examples of drugs like that.
Smith said some drugs being tested in phase III clinical trials appear to work even better than the chemotherapies currently available. Also on the horizon are greater advances in tailoring chemo to the biology of an individual's tumor.
Schilsky said the new-generation drugs are moving patients further away from the image many people have of chemotherapy.
Years ago he regularly observed chemo patients hovering over a wash basin and vomiting during treatment. By contrast, he recently peeked in on a patient tethered to an IV who was undergoing chemo as he enjoyed a sandwich.
"It was remarkable," Schilsky marveled, to see him "eating lunch and getting this drug."
John Bailey, 58, who was first diagnosed with cancer nine years ago, has been taking Nexavar for three years to treat non-secretory neuroendocrine tumors in his liver. Cancer cells migrated there from his duodenum, part of the small intestine.
The tumors have shrunk somewhat, he said, and side effects of the drug, which he takes in pills, have been minimal.
"When people see me they can't believe I have cancer," Bailey said. "They say I look so healthy."
The main side effect for Bailey has been minor calluses on his fingertips and feet. That is a big change from the experiences of friends diagnosed with cancer years ago. Prescribed early-generation chemo drugs, they "seemed to wither away," he said.
"I feel fantastic," said Bailey, a regional international sales manager for UPS. "I haven't missed a day of work. I'm out the door by 5:30, 6 o'clock. I'm one of the first to arrive and many nights I turn out the light."
Dr. Mark Ratain, who oversees a clinical trial of Nexavar at the University of Chicago, where Bailey receives the drug, urged people to participate in research so they can gain access to promising new treatments.
"We're stuck fighting a war on cancer when we should think in terms of arriving at a truce," Ratain said. "That's what this drug allows: You don't bother me and I don't bother you."
The effectiveness of anti-cancer drugs in saving lives varies widely depending on the type of cancer, the stage of disease and other individual factors. Dr. Jamie Von Roenn, a medical oncologist at Northwestern Memorial Hospital, gave these examples:
Germ cell tumors of the testes (testicular cancer) are almost always successfully treated, even when the cancer has metastasized.
Some types of leukemia are successfully treated, but not all.
Those with advanced lung cancer might see some benefit in longer life expectancy.
Those with metastatic breast cancer can experience higher quality of life and longer life but are not cured.
Symptoms of pancreatic cancer can be relieved, but patients don't live significantly longer.
Chemo is not curative for some non-Hodgkin's and Hodgkin's lymphomas, but patients might gain some time and symptom relief.
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© 2009, Chicago Tribune; McClatchy-Tribune Information Services.