Originally created 04/01/97

Treatment for cancer of ovary shows promise



Cancer of the ovary is one of the most dismal of all malignant tumors - difficult to detect early and fatal within five years in 65 percent of patients. But an aggressive new treatment has produced a striking improvement in survival for some women with advanced ovarian cancer, and it is about to be tested in a national trial.

In the experimental treatment, blood-producing cells, called stem cells, which normally reside in the bone marrow are "harvested" from a patient and frozen for later use.

The patient then receives a combination of chemotherapy drugs in very high doses - a regimen designed to kill all remaining tumor cells, but also lethal to bone-marrow cells. Several days later, the patient's frozen stem cells are thawed and transfused back into her circulation, along with growth factors that stimulate the cells to multiply and regenerate the bone marrow.

For most women in the study the new regimen apparently offered little improvement in survival over current treatments. But for about 20 percent of patients - those who had small amounts of tumor and whose cancer cells were sensitive to the platinum-based drugs that are the mainstay of the chemotherapy - the aggressive regimen lengthened survival significantly compared with current therapies.

For that group of patients, "we show a far superior survival rate than any other salvage therapy has ever shown in this disease," said Robert Bayer of Loyola University of Chicago Medical Center, who presented the new results in March at the annual meeting of the Society of Gynecologic Oncologists in Phoenix.

Cancer of the ovary strikes more than 26,000 American women each year and kills almost 15,000. In three-quarters of the cases, the cancer has spread outside the pelvis, to the abdomen or other regions of the body, by the time it is discovered. The tumor cells typically implant themselves in many locations, and the track record of current treatments is extremely poor.

Bayer said that until Taxol, a chemotherapy drug, was approved for use a few years ago, only about 20 percent of women with ovarian cancer were alive five years after diagnosis. Even now, of patients treated with standard combinations that include Taxol and platinum-containing drugs, only about 35 percent survive for five years. Bayer said patients often respond favorably to an initial course of chemotherapy, but in the majority, the tumor persists or recurs. Many women then undergo a succession of operations or repeat courses of chemotherapy, only to have the cancer return each time within a few months.

"It's terrible," he said. "The quality of life for the typical patient with ovarian cancer is misery."

Viewed in that context, the new results are heartening enough to persuade Bayer and other researchers that high-dose chemotherapy must be tried earlier in the course of the disease and must be tested against standard treatments in a large national study. In January, the National Cancer Institute launched such a trial, which is designed to enroll about 275 women at medical centers across the country.

In the results reported this week, 100 women with advanced ovarian cancer underwent the high-dose treatment, followed by bone-marrow or stem-cell transplants, at Loyola, a medical center in Maywood, Ill. All of the women had suffered recurrence of their cancers after previous chemotherapy, but in some, the amount of tumor present was very small or microscopic - detectable only by a blood test. High doses of three different drug combinations were tried, including two containing platinum-based drugs and one containing Taxol.

For the entire group, the median time from treatment to recurrence of tumor was seven months, and median overall survival was 13 months. However, in the subgroup of patients with the small, platinum-sensitive tumors, the median time from treatment to recurrence was 19 months, and median overall survival was 30 months.

Bayer said those figures are better than for any other therapy for advanced ovarian cancer and compare well with results from high-dose chemotherapy for other tumors, such as lymphoma and cancer of the testicle or breast.

The next step, he said, is to test the treatment in women who have just finished their initial surgery and chemotherapy for ovarian cancer. The national trial is to enroll 275 patients who still show evidence of disease after this initial treatment, and will randomly assign them either to standard chemotherapy or to high-dose, three-drug therapy followed by a stem-cell transplant.

"That's the best chance to intervene," said Bayer. "Whether to intervene with standard chemotherapy or (high-dose therapy and) transplant is the major argument. This is a critical question in this disease."

The high-dose therapy is risky. Twelve patients died during treatment at Loyola, most from infections but four from drug-related heart damage or kidney failure. Bleeding is also common. Bayer said the number of deaths was not unusually high for patients with advanced cancer undergoing stem-cell transplants.