Chemo that's easier to take

Times Staff Writer

As millions of people know firsthand, cancer survival often comes with a price. New therapies can extend patients' lives, in many cases to an extent unimagined a generation ago, but the treatment itself -- particularly chemotherapy -- can be grueling.

The accompanying nausea, vomiting, fatigue and hair loss have become synonymous with cancer treatments. Some patients who are recommended for chemotherapy actually decline it, even when doing so decreases their chances of a cure.

The recent advance in ovarian cancer therapy highlights the paradox of today's treatments. Earlier this month, the National Cancer Institute announced that a chemotherapy regimen for women with ovarian cancer greatly improved survival rates. Buried in the good news, however, was the fact that only two of every five women in the study were able to complete the treatment because of side effects.

"You can understand why chemo has a bad reputation," says Dr. Edward Trimble, chief of gynecological cancer therapeutics at the National Cancer Institute. "You lose your hair, and you're sick as a dog."

But the effort to ameliorate chemotherapy's side effects is showing some signs of progress. With cure rates improving for many types of cancer, says Dr. Julie Gralow, an associate professor of medical oncology at the University of Washington, doctors have grown more comfortable trying to mitigate side effects. They're using three basic strategies: administering less-toxic drugs, adjusting the chemo regimen and providing better "supportive care," meaning medications to stave off nausea and other side effects along with advice on exercise, nutrition and emotional support.

The ovarian cancer study offers an example of the changes that are possible when doctors focus on reducing side effects. In that study, the women received the chemotherapy through a port directly into their abdomen -- a delivery method even tougher than traditional intravenous chemotherapy. But doctors familiar with the study point out that intra-abdominal therapy -- as well as traditional chemotherapy -- can be made easier.

"We've been able to dramatically decrease the incidence of side effects and help people live fuller lives during the time they're getting chemo," Trimble says. "Some patients are able to continue working and continue with all of their family responsibilities."

The first step is to complain. Many patients feel they most soldier on stoically, that misery is par for the course. If that's the case, speak up, Trimble suggests.

"We want people to tell us how they're feeling so we can figure out how to help them through the day," Trimble says. "And doctors need to ask [about side effects]. Patients want the best treatment for their cancer. They may think 'I'm going to have to suffer for this.' "

As Gralow says: Lowering the misery index has become a priority for doctors in the last decade.

Chemotherapy consists of substances that essentially poison cancer cells to kill them. But the drugs cannot distinguish between cancer cells and normal cells. The side effects -- diarrhea, vomiting, fatigue, infection, mouth sores, nerve damage -- are typically the result of damage to normal cells.

It is still impossible to predict who will have problems and who will sail through therapy virtually unscathed, but doctors have identified which drugs are less likely to cause problems. Chemotherapy can also be given in small doses and at various time intervals to reduce the chances of post-treatment misery. The method used to deliver the drugs -- intra-abdominal, intravenously or orally -- also can make a difference.

In the study on ovarian cancer, published earlier this month in the New England Journal of Medicine, researchers found that women who received the chemotherapy drugs Taxol and cisplatin directly into the abdomen -- which is also called intraperitoneal delivery -- survived an average of 16 months longer than women who had traditional intravenous chemotherapy (66 months versus 50 months). The regimen is thought to work better because the drugs stay in the system longer.

But the women having intra-abdominal therapy were plagued by problems with the port (the tube inserted to deliver the drugs) as well as nausea and pain from having as much as two liters of fluid pumped directly into the abdominal cavity. Patients were also more likely to have liver and kidney problems and nerve damage.

The problems raise a legitimate question, says Dr. Lynda Roman, an associate professor of gynecology at USC. "Was it worth the torture?

"It is so difficult," she says. "But you can change it to make it more tolerable. There are tricks. And lengthened recoveries can occur."

USC doctors have used the intraperitoneal approach for almost 15 years for ovarian cancer, she says, often adjusting the regimen to make it easier for patients. Reducing the dosages and having patients stay hydrated can also help lessen side effects, Trimble says.

"Since that study was undertaken, we've gotten smarter about giving intraperitoneal therapy," he says.

Similarly, doctors can also make adjustments in intravenous chemotherapy by using smaller doses or varying the timing of the doses.

Teresa Pan, 46, underwent six intravenous chemotherapy sessions followed by six intra-abdominal sessions at USC after her diagnosis of advanced ovarian cancer in 2001. Pan, who is married and has a daughter, found that chemotherapy wore her down: first physically, then mentally.

"When you're on chemo, you have emotional ups and downs," she says. "When your physical strength is not there, your emotions kick in and you start wondering, 'Am I going to make it or not? What will happen to my family? What about my daughter?' "

Pan relied on exercise and nutrition to battle nausea and fatigue. Now fully recovered, she's glad she toughed it out. "The results were wonderful. I pulled through."

Drug companies have also come to the aid of chemotherapy patients in the last decade, introducing several medications to help reduce nausea, infection and anemia.

Some patients, however, find they cannot afford, or their insurance will not cover, the newer, more powerful drugs for side effects, Gralow says. Doctors and patients may need to be persistent in trying various medications and working with an insurance plan to obtain the needed relief, she says.

Researchers continue to look for cancer drugs that preserve a patient's quality of life. Studies are underway, for example, on a medication similar to Taxol (which is used for breast, ovary, lung and several other types of cancers) that doesn't seem to cause the severe hair loss typical of most chemotherapies. And a drug approved for metastatic breast and colon cancer, called Xeloda, doesn't cause any hair loss.

An emerging approach to treating cancer based on genetic information, called targeted therapy or molecular therapy, may ultimately prove to be more effective and less taxing than chemotherapy. By studying the genetic makeup of a tumor, doctors can predict which tumors are more aggressive and select treatments accordingly.

And, says Gralow, "understanding the genes is important because it allows us to make drugs targeted specifically to those genes and the proteins they produce."

For example, the drug Herceptin works well and has minimal toxicity in breast cancer patients who carry the HER-2 gene. Avastin, a targeted therapy approved for colon cancer treatment, also causes little nausea or changes in red and white blood cells.

Many other targeted therapies are in the pipeline.

"These new biologically targeted therapies that are tumor specific are going to decrease side effects," Gralow says. "And fewer people will need chemo."

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