- The Washington Times - Tuesday, April 16, 2002

Peggy Gardiner of LaPlata, Md., knows all too well the ups and downs of hope and despair in the detection and treatment of ovarian cancer.
This deadliest of several gynecologic cancers strikes one out of 57 women, with the majority of cases found only in later stages, when survival rates are poor, according to the Washington-based Ovarian Cancer National Alliance.
Fresh hope arises almost daily in studies announcing new findings about the behavior of cancer cells and possible ways to kill or circumvent them, but the cruel reality is that such innovative approaches often self-destruct or take many years to become acceptable in mainstream medicine.
The situation has prompted the alliance to push a program of awareness emphasizing the "subtle" rather the "silent" aspects of the disease and to try to correct a key misimpression many women have about the Pap smear a routine screening in most women's pelvic exams. The Pap smear does not detect ovarian cancer, though many women think it does. (It is used to detect cervical cancer, more easily found and treated and hence less fatal.)
Mrs. Gardiner, 67, is in what is known technically as "the second line" a recurrence of cancer following surgery and initial rounds of chemotherapy. Her story is one that is all too familiar to health professionals involved in oncologic research and treatment. In many ways, it represents the frustration they feel when up against the wily nature of their opponent.
Her mother died of the cancer 12 years ago at the age of 81, indicating that Mrs. Gardiner eventually might be affected as well. When it is detected early and treated properly, survival rates are as high as 90 percent. That is reassuring only if the cancer is found early enough, and symptoms often are elusive at best.
The standard list of indications includes unusual abdominal bloating, pressure or discomfort; nausea, indigestion or gas; constipation, diarrhea or frequent urination; abnormal bleeding; unusual fatigue; unexplained weight loss or gain; and shortness of breath.
(In addition to staying alert to one's own body, strategies said to help reduce the risk of acquiring ovarian cancer include bearing a child and breast-feeding, taking oral contraceptives, exercising regularly and having a tubal ligation.)
Women who switch suddenly to a new diet might experience some of these same symptoms, concedes researcher Sarah Olson of New York's Memorial Sloan-Kettering Hospital, who headed up a study on the subject and says "almost all women with ovarian cancer have symptoms." It's "the constellation" of them and "the constancy factor" that count, she says, acknowledging that women with "sensitive stomachs" may be prone to regular body changes or have a bloated feeling just before a menstrual period.
Mrs. Gardiner says she had no warning none of the usual symptoms that cancer was present.
Knowing she was at risk women older than 50 are in danger whether or not there is a family history of cancer she had gone to her family doctor in November as usual for a physical exam. Every few years, too, she would get a blood test known as CA125 (after a protein molecule marker present in the blood of many women with the cancer). However, CA125 isn't considered a good screening tool for ovarian cancer because it produces a large number of false positives and it can't tell if a tumor is malignant or not.
Mrs. Gardiner's doctor, who knew her family history, recommended that she undergo further testing; a transvaginal sonogram subsequently revealed that Mrs. Gardiner indeed had what she describes as "an ovarian mass."
Dr. James Barter, a professor of obstetrics and gynecology in the division of gynecologic oncology at Georgetown University Medical Center, operated last August. He removed Mrs. Gardiner's ovaries and ordered chemotherapy a combination of Taxol and carboplatinum delivered intravenously to kill off any remaining cancer cells and help prolong her life.
A second surgery done to check the progress of the anti-cancer drug showed no tumor growth, but Dr. Barter found some cells that apparently had not responded to treatment. He then changed to a newer form of the drug that, like Taxol, is derived from taxanes found in the Eastern and Western yew tree.
Mrs. Gardiner has had five rounds of chemotherapy, a toxic medicine, and, at one point participated in a drug-study trial that involved using nose drops three times a day. The latter contained a substance intended to increase the body's immune response to cancer and decrease cancer's ability to recruit new blood vessels.
"It wasn't as good as we had hoped," Dr. Barter says. In addition, he reports that the Seattle company that made it went bankrupt.
He may try next a different chemotherapy compound produced by a Japanese company that he says "in essence works by gumming up the DNA."
"I'm doing well, but at times I don't feel exactly right," Mrs. Gardiner says in her postoperative phase. "Chemotherapy has different effects, but you are given medication for nausea." She bought a wig when her hair started falling out and kept up with a normal life as much as possible.
Her spirits are good. "It's on your mind a lot," she says, "but I think you have to go on as much as you can with normal things. I wouldn't like this to be my complete focus, to make cancer the center of my life. I don't want to think of leaving the world too soon."
Before the operation, she had spent nine years as a volunteer in a hospital helping with dying patients and their families. "Maybe I will get back to that, but for the moment, I don't want to deal with it. It's kind of hard to plan [activities]," she says. "I'm not as dependable as I should be."
These days, she helps two days a week in the office of her husband's business, which deals in farm equipment sales and service.
The medical profession is "now working on other blood tests that are more reliable" for screening, says an upbeat Mrs. Gardiner. She is referring to a well-publicized recent report showing how patterns of proteins, called proteomics, can detect the presence of ovarian cancer before clinical symptoms appear. Blood for the test, which relies on an advanced software program, can be obtained from a finger prick.
The method, which must go through several trials, won't be available for at least two years, Dr. Barter says. "Proteomics is just one of many things we can hope for," he notes. "We've improved the quality of life [for patients] and survival rates by using different chemotherapy agents in the last 15 or 20 years. The problem is there are still late recurrences."
The proteomics study, which was conducted by the National Cancer Institute, the Food and Drug Administration and Correlogic Systems Inc. of Bethesda, is the latest and most promising detection method. Early detection of ovarian cancer is crucial because 90 percent of patients live more than five years when the cancer is caught in its early stages, but nearly three-quarters of the cancers are not detected until much later, when the five-year survival rate is only about 25 percent.
To date, surgery and chemotherapy are the only means of treatment, but researchers are working on new methods and, just as important, on prevention.
OvaRex, made by AltaRex, is the trademark name of a promising therapeutic agent that is in the final stages of development to treat advanced ovarian cancer.
The protein, given in an IV solution, is a vaccine antibody, made similarly to a smallpox vaccine. It stimulates the production of cells in the body to go after cancer cells, says Dr. Alan Gordon of the Sammons Cancer Center, which is part of Baylor University Hospital in Dallas.
"The drug itself has been found to be extremely safe compared to standard chemo since it doesn't have side effects," he says.
Just as promising in the area of prevention are studies being done with birth control pills. Prevention is critical, says Dr. Gustavo Rodriguez of Northwestern University Medical School System.
"Ninety percent of ovarian cancers occur sporadically, unrelated to risk," and "the risks and side effects of surgery aren't insignificant," Dr. Rodriguez says. Plus, he points out, the chances of cancer cells being resistant to chemotherapy methods are high.
"If a woman takes a pill for as little as three years, there is a 30 to 50 percent reduction in her chances of getting ovarian cancer," he says. "Data we have show the protective effect persists for as long as 20 years or more after use."
The progestin component in the pill acts as a suicidal agent in dramatic ways, he says, showing a "lowered risk of 70 percent," although he is cautious about making recommendations "because for any one person, it is an individual decision based on her medical issues, lifestyle habits and risk factors. We need to develop something all women can take."
Ann Kolker, executive director of the Ovarian Cancer National Alliance, a "five and a half-year survivor," is intent on getting Congress to increase funding for further study of the proteomics detection test. Meanwhile, she says, "the tag line is until there is a test, awareness is best."
Alliance figures show that the National Cancer Institute spent nearly $70 million in 2001 on ovarian cancer research, compared to $407 million on breast cancer research, $150 million on lung cancer research and $136 on prostate cancer.
Rep. Rosa DeLauro, Connecticut Democrat and an ovarian cancer survivor, is appealing to colleagues to support a separate Department of Defense ovarian cancer research program costing $15 million as part of the House Defense Appropriations Bill for 2003, or $3 million more than the Defense Department earmarked for the program last year.

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