Unusual weapon touted in ovarian cancer fight

A little-used treatment extended the lives of women with advanced ovarian cancer 16 months longer than standard chemotherapy in a major clinical trial, an unusually significant benefit for a cancer therapy.

Anticipating the study published in today's New England Journal of Medicine, the National Cancer Institute issued a statement yesterday encouraging doctors to start offering the therapy to women immediately, and some Massachusetts hospitals plan to train doctors and nurses and set aside space to provide this more complicated and expensive type of chemotherapy.

The treatment involves dripping chemotherapy directly into the abdomen, instead of into veins as is usually done. This allows physicians to expose the area surrounding the tumor to higher concentrations of medicine, while normal tissues, such as bone marrow, are spared.

''This is a very, very significant step in the treatment of advanced ovarian cancer. There is no doubt about this," said Dr. Ursula Matulonis, director of medical gynecologic oncology at the Dana-Farber Cancer Institute, who was not involved in the study. ''I will recommend this to patients, and we will start offering it this week."

Patients who choose the therapy, however, may pay a price for a longer life: Study participants who had the medicines dripped into their abdominal cavities, called intraperitoneal therapy, suffered more severe and more frequent side effects during and right after treatment, including infections, stomach pain, and numbness and tingling in their fingers and toes. Just 42 percent of the 205 women started on the therapy were able to withstand the 18 weeks of treatment.

Ovarian cancer is the fourth deadliest cancer for women, following cancers of the lung, breast, and colon. About 22,000 women in the United States were diagnosed with ovarian cancer last year, and about 16,000 died of the disease.

Ovarian cancer usually is fatal because three-quarters of patients are diagnosed after the cancer has spread; women experience few symptoms in the early stages, and there is no screening test. After surgery and standard chemotherapy, most women experience a remission, but the cancer eventually spreads to other organs.

In the study, led by Dr. Deborah Armstrong at Johns Hopkins Kimmel Cancer Center in Baltimore, women who had standard, intravenous chemotherapy lived four years on average. Women who got intravenous along with abdominal chemotherapy lived an average of five years, four months. All 415 women in the study, which occurred at dozens of US hospitals, had Stage 3 ovarian cancer, meaning it had spread beyond the pelvis, and had surgery to remove almost all of their original tumor.

Women in both groups were treated aggressively. Those in the intravenous group received one chemotherapy drug, paclitaxel, over 24 hours followed by another medicine, cisplatin, the next day, both intravenously. Women in the test group also got paclitaxel intravenously the first day, but then on separate days a week apart received paclitaxel and cisplatin through a catheter inserted in their abdomen. Treatments were repeated every three weeks over 18 weeks, for a total of six courses of treatment.

Injecting chemotherapy into the abdomen helps the drugs reach the tiny tumors hidden inside the abdominal cavity and on other organs in advanced ovarian cancer. But the higher doses and concentrations of medicine also make the therapy more toxic.

For example, some women who received abdominal chemotherapy developed numbness in their fingers and toes that was so severe they had trouble buttoning a blouse, eating with a fork, or walking, said Dr. Harrison Ball, chief of gynecologic oncology at UMass Memorial Medical Center in Worcester, which participated in the study.

Still, he said, the therapy extends patients' lives so significantly that he will recommend the treatment to his patients.

After a year, most patients in the study who had received abdominal therapy reported a similar quality of life to patients in the control group, meaning the side effects were temporary.

Dr. Stephen Cannistra, an oncologist at Beth Israel Deaconess Medical Center who wrote an editorial accompanying the study, said the high drop-out rate among women who received abdominal chemotherapy makes the results all the more remarkable: Though most women did not receive the full course of abdominal treatment, the group as a whole still outlived the group receiving only the standard therapy. Women who stopped the abdominal treatment switched to only intravenous therapy.

''I suspect that many patients are going to be willing to go through it even with the greater potential for side effects," he said in an interview. Cannistra wrote in his editorial that the improved survival ''is one of the largest benefits ever observed for a new therapy in gynecologic oncology."

Oncologists eventually may be able to give abdominal therapy with less toxic drugs or for a shorter duration, doctors said.

Therapy given this way is not a new idea; doctors have debated it for decades. But most physicians have resisted the treatment, partly because it's more difficult and expensive to administer. Patients must be closely monitored for dehydration and other side effects, they require more visits and call more often with questions and complaints, and they require surgery to insert the catheter. Also, previous clinical trials of abdominal therapy have not been convincing.

Now, many oncologists predict that abdominal therapy along with intravenous chemotherapy will become standard care for advanced ovarian cancer patients, but they said such a change will require intensive training and education of hospital medical staff and community oncologists.

Some patients, including those with other medical problems such as kidney disease, may be too sick to qualify for this approach.

At Dana-Farber and Brigham and Women's Hospital, which have a partnership to treat cancer patients, Matulonis said doctors initially will admit ovarian cancer patients to the hospital overnight for abdominal chemotherapy, at least at the start of their treatment, requiring the hospital to train nurses in the procedure.