An Aggressive Approach to a Most Deadly Disease

Six months after extensive surgery to remove ovarian cancer, Joanne Jensen of Burbank checked back into the hospital for a “second look” surgery, to see if any traces of cancer remained.

The news was almost good. Of 50 tiny tissue samples, one contained microscopic cancer cells.

What Jensen opted to do next is on the cutting edge of cancer treatment, particularly for ovarian cancer. Instead of checking back into the hospital for another round of standard chemotherapy, she gave her doctors the go-ahead to try an investigational therapy that has become popular for women with advanced breast cancer: very high-dose chemotherapy and bone marrow transplantation administered on an outpatient basis.

The effectiveness of this therapy is still considered unproven for breast cancer. Even so, oncologists are increasingly compelled to try it for ovarian cancer because of the lack of progress in treating the disease, one of the most deadly types of cancer.

“This is a bad disease,” says Jensen, 55, who had the high-dose chemo in March and is already back at work teaching middle school. “But I’ve had the latest treatment for this type of cancer.”

The therapy Jensen received also exemplifies how medical advances are being applied in an era when insurers refuse to open their checkbooks for anything deemed unproven--especially if it costs a lot.

Hospitals are increasingly offering the exorbitantly expensive high-dose chemotherapy and bone marrow transplantation on an outpatient basis to curb costs. While insurers generally now cover the therapy for breast cancer patients--after years of patient protests and several high-profile court battles--most women with ovarian cancer are still turned down.

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Bone marrow transplantation--or a variation called peripheral blood stem cell transplantation--has increased dramatically in the treatment of several types of cancer.

Traditionally, bone marrow has been donated by family members or unrelated donors to treat cancers of the blood, such as leukemia and lymphoma. The patient first undergoes intense treatment to kill all blood-forming cells, including the cancer, and then is reinfused with donor marrow to produce healthy, cancer-free blood cells.

Autologous transplantation--using the patient’s own bone marrow or stem cells--has become popular for tumors of the breast, testicle and ovary. Autologous bone marrow transplantation (ABMT) for these cancers isn’t a treatment but allows doctors to bombard the patient with much higher doses of chemotherapy than have been previously attempted. Very high doses of chemotherapy can destroy the blood’s capacity to regenerate.

“What has limited us to high chemotherapy doses is the toxicity it has on the bone marrow. The lower the blood counts, the higher the risk of infection or bleeding,” says Dr. Linnea Chap, an oncologist at UCLA’s Jonsson Comprehensive Cancer Center who treated Jensen as part of a study.

Removing bone marrow or peripheral stem cells before chemotherapy and then reinfusing it afterward reduces the risks associated with high-dose chemo.

“The diseases that you would look at using this concept for are those that are chemo-sensitive, and if you increase the doses of chemo you are more likely to get a bigger response,” Chap says.

Some doctors are so enthusiastic about the treatment that they are recommending high-dose chemotherapy and ABMT for some patients upon the initial diagnosis. Until recently, high-dose chemo and ABMT was considered a last-resort therapy for patients who had a recurrence of cancer and had exhausted all other options.

The other trend is the use of ABMT for ovarian and testicular cancers.

“With the success we’ve seen with breast cancer, we are applying it more to ovarian and testicular cancer,” Chap says.

But, Dr. Robert O. Dillman, medical director of Hoag Cancer Center in Newport Beach, says: “It has certainly not been accepted for ovarian cancer with the same enthusiasm for which it has been accepted for breast cancer.”

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Although many insurers now cover ABMT for breast cancer treatment, its use remains controversial because it is still considered investigational. A U.S. Government Accounting Office report released last month contends that scientific evidence is lacking that high-dose chemotherapy and ABMT is more effective than standard breast cancer therapies. Four government-sponsored studies on this question are now underway.

Nevertheless, the treatment for breast cancer has grown from an estimated 522 cases in 1989 to 4,000 cases in 1994, the GAO reported. The treatment is costly, ranging from $65,000 to more than $100,000.

There is even less evidence that high-dose chemotherapy and ABMT works for women with ovarian cancer. But according to many gynecological oncologists, investigational approaches are required against a disease as nasty as ovarian cancer.

Ovarian cancer is diagnosed in about 26,000 American women each year. Often detected only after the cancer has reached an advanced stage, the five-year survival rate is an abysmal 44%, according to the American Cancer Society.

If diagnosed and treated early, the five-year cure rate is 91%. But according to a study released last month from the National Cancer Institute, 90% of women who have surgery for early-stage ovarian cancer are not checked thoroughly by surgeons to see if the cancer has spread to the abdomen or nearby lymph nodes. If the cancer has spread, chemotherapy is recommended.

In cases of advanced ovarian cancer, extensive surgery is usually followed by four to six months of standard-dose chemotherapy.

But the fact that standard therapies for advanced ovarian cancer are so often unsuccessful makes high-dose chemo and ABMT a reasonable approach, Dillman says.

“The biggest obstacle to this field moving forward is the reluctance by insurers to pay the bill,” he says. “The science behind it is so strong and our options are so dismal that you can’t justify not doing this.”

And, says Chap: “If you look at the last 20 years with ovarian cancer, not a lot of progress has been made. It’s definitely something we need to delve into.”

Her research project--with colleagues John Glaspy and Beth Karlan--is open to women with recurrent ovarian cancer as well as those with newly diagnosed cases.

“If this is going to work, ultimately it should be done upfront--right after a patient has been diagnosed and had surgery or after a first round of chemo--and not wait for a relapse to happen,” Chap says.

Many of the women who have opted for high-dose chemo and ABMT for ovarian cancer have paid for the treatment themselves. Doctors have attempted to reduce costs by offering the therapy on an outpatient basis.

In Chap’s protocol, the patient has surgery to remove the cancer. After recovering, the patient’s peripheral stem cells are filtered from the blood and frozen. The patient then undergoes two to four high-dose chemotherapy treatments as an outpatient, at 25-day intervals. After chemotherapy, the stem cells are thawed and re-injected into the blood to restore the blood count and immune system.

“We wanted to see if we could bring down the cost,” says Chap of the outpatient approach. “But one of the interesting things to me was that breast cancer patients were in the hospital and bored to death. I don’t know how often patients would say, ‘I could be home for this.’ Well, why not let them go home?”

Patients who undergo ABMT have very weakened immune systems and must avoid germ-ridden environments, experts says. Home is the best place for that.

“The most dangerous place with a person with an impaired immune system is the hospital,” Dillman says. “The organisms one acquires in the hospital are more virulent.”

Outpatients must take some precautions, such as consuming a low-bacteria diet (no fresh fruits or vegetables that can harbor bacteria), thorough hand-washing and wearing a mask when traveling to and from the hospital for check-ups.

Complications or side effects sometimes force patients into the hospital, Dillman says. And it’s too soon to say how much outpatient high-dose chemotherapy and ABMT saves in costs.

In terms of comfort, however, patients like the setup and the hope the aggressive therapy gives them, Chap says.

“We’ve had five patients. All of the patients have done quite well and have unanimously said they liked being at home,” Chap says.

Jensen says the early days of the treatment were nerve-racking. As an outpatient she did not have the reassuring presence of nearby nurses.

“I had to report any suspected fever or pain, and I felt very responsible for myself,” Jensen says. “Also, my husband had to be a full-time caretaker. By the second month I was more at ease.”

She took advantage of a computer online support group for women undergoing chemotherapy, and she relied heavily on her religious faith and the prayers of family and friends, Jensenadds.

Jensen was especially fortunate to get insurance coverage of the treatment.

“I feel lucky the insurance company was enlightened enough to do this,” she says. “I’m back at work now, and my life is almost normal.”