New Therapy for Cervical Cancer Cuts Death Rate

Radiation and chemotherapy in combination can reduce the death rate from advanced cervical cancer by 30% to 50% compared to the use of radiation alone, the National Cancer Institute said Monday in a letter sent to thousands of physicians who treat cancer.

About 12,800 women in the United States will contract cervical cancer this year and about 4,800 will die of it. The current standard of therapy is surgery followed by radiation if the tumor has spread locally, or chemotherapy alone if it has metastasized throughout the body.

The institute’s recommendation that radiation and chemotherapy be used concurrently--the first change in cervical cancer therapy in 20 years--arises from five separate studies conducted independently on more than 1,800 women at cancer centers nationwide. It is only the fifth time in the institute’s history that it has issued such a letter to physicians.

Three of the studies are scheduled to be published in the New England Journal of Medicine on April 15, but the institute took the unusual step of requesting that they be released early because of their public health impact. The other two studies will be published later this year.

“Anything that improves survival in any kind of advanced cancer is a major improvement,” said Dr. John Glaspy, director of UCLA’s Bowyer Oncology Center at the Jonsson Comprehensive Cancer Center. “It’s not very often that we make an advance that has that kind of implication. That is why cancer doctors are excited about it.”

The change in therapy will have a sweeping impact on women’s health because many cervical cancer victims are relatively young, between 25 and 50, said Dr. Peter G. Rose of the Case Western University School of Medicine, who led one of the studies.

“When a woman dies at the age of 30, the impact is devastating to her family and to society in general,” Rose said.

As many as 93% of all cases of cervical cancer are caused by infection with one of several strains of the human papilloma virus--although experts caution that most such infections do not proceed to cervical cancer. Other risk factors include cigarette smoking and sex at an early age.

Mortality from cervical cancer in the United States has decreased dramatically, by 75% or more, since the development 45 years ago of the Pap smear, which detects it in its earliest, most curable stage.

Fifty percent of the women who develop invasive cervical cancer have not had a Pap smear in the preceding five years, according to the institute.

Unless cervical cancer has metastasized throughout the body, the normal course of treatment is surgical removal of the tumor followed by local radiation. As recently as three years ago, an institute panel recommended that chemotherapy not be used in such cases because it did not appear to be effective.

The most commonly used medication at that time was hydroxyurea, and the new studies confirm that its use provides only modest improvements over radiation alone.

But the new studies involved the use of the drug cisplatin, either alone or in combination with 5-fluorouracil, and those anti-cancer drugs provided a major improvement in survival.

“We think the data are so compelling that this should change the way women are treated all over the country and, indeed, around the world,” said Dr. Edward Trimble of the National Cancer Institute.

In three of the five trials released Monday, women were randomly divided into groups that received either a combination of surgery and radiation or the same treatment with the addition of chemotherapy. In one of those three trials, the women received only cisplatin, while in the other two they received cisplatin and 5-fluorouracil.

In all three studies, the proportion of women alive after three years was higher in the groups receiving chemotherapy plus radiation than in those groups receiving radiation alone.

In the other two studies, all women received surgery, radiation and chemotherapy. But some received hydroxyurea, while others received either cisplatin alone or in combination with 5-fluorouracil.

In both of these studies, the women who received cisplatin had higher survival rates.

The main side effects of the combined therapy in all the studies were leukopenia (a low number of white blood cells), nausea and vomiting. These were more frequent and severe in the women who received chemotherapy than in those who got radiation alone. Hair loss did not occur as a result of the chemotherapy with these drugs, which was welcome news to the women.

The researchers are not completely sure why the combination works better than radiation alone. It is likely that the drugs make the tumors more susceptible to the killing effects of radiation, Glaspy said. They also may kill micrometastases--small clusters of cancer cells that have spread elsewhere through the body--reducing the likelihood of a relapse.

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Facts About Cervical Cancer

* An estimated 12,800 cases of cervical cancer will be discovered in the United States this year and 4,800 women will die of the disease.

* The incidence of cervical cancer in the United States has dropped by 75% in the 45 years since the introduction of the Pap smear for detecting it early. But about 20% of all American women have not had a pap smear in the last three years, and 50% of those with invasive cervical cancer have not had one in the preceding five years.

* For U.S. women, the incidence is about 8 cases per 100,000 population.

* Worldwide, an estimated 400,000 cases occur each year, making it one of the most common forms of cancer.

* The primary risk factor is infection with the human papilloma virus.

Source: National Cancer Institute