The benefits of combining chemotherapy with radiation therapy were illustrated in five large-scale clinical trials with a total enrollment of 1,700 women who had invasive cervical cancer. The studies were conducted by three of the National Cancer Institute’s (NCI) Clinical Trials Cooperative Groups, consortiums of institutions and physicians that conduct trials jointly. The results of the studies will be published in the April 15, 1999, issue of the The New England Journal of Medicine.

The Evidence

The evidence was so strong, the NCI took the unusual step of mailing clinical announcements to thousands of physicians around the country, urging them to give strong consideration to adding chemotherapy to radiation therapy in treating invasive cervical cancer.

"The findings of these five trials are remarkably consistent. They are likely to change the standard of care for invasive cervical cancer," said Richard D. Klausner, MD, NCI director.

All the trials compared one treatment to another. Three different drugs were used in combination with radiation therapy. The drug cisplatin was used in all the trials. Scientists also studied the effects of hydroxyurea and 5-fluorouracil (5-FU) either alone or in combination with cisplatin.

Patients who received cisplatin or cisplatin/5-FU in combination with radiation had increased rates of survival. Researchers say further studies are necessary to determine the best chemotherapy, because they are not sure if cisplatin alone or cisplatin combined with 5-FU or another drug is the optimal chemotherapeutic treatment to add to radiation therapy.

"These are all excellent studies. They are large-scale, prospective randomized trials examining the use of chemotherapy in several different clinical situations in women with cervical cancer. In all five trials, there was a significant benefit to the chemoradiation approach," said Stephen C. Rubin, MD, professor and chief of the Division of Gynecologic Oncology at the University of Pennsylvania Health System.

Changing the Standard of Care?

"These studies should change the standard of care. Strong consideration should be given to the use of cisplatin-based chemotherapy in women undergoing radiotherapy for cervical cancer," Dr. Rubin added. "Women with cervical cancer, particularly those with advanced stage disease, can expect a significant improvement in their chances for cure."

Treating women who have invasive cervical cancer with a combination of radiation and chemotherapy is not a completely new concept. In the mid-1980s several smaller studies were begun, one of them by Carolyn Runowicz, MD, director of gynecologic oncology at Albert Einstein College of Medicine and Montefiore Medical Center in New York.

"We found the combination of cisplatin and radiation was tolerable and had a good long-term outcome for patients. So we were not surprised by these new findings, because we believed our work. And that’s been validated by these large-scale random trials," Dr. Runowicz said.

The American Cancer Society estimates 12,800 new cases of invasive cervical cancer will be diagnosed in the US in 1999, and 4,800 women will die of the disease. Dr. Runowicz said, "The most important message for women is this: if they get regular Pap smears and follow up on any Pap smears that are not normal, they can almost prevent cervical cancer from occurring."

Regular Pap test screening ensures most cervical cancers are found when they are at a very early and treatable stage. The ACS recommends women begin having annual Pap tests at the age of 18, or at the onset of sexual activity. After three or more consecutive normal findings, the Pap test may be performed less frequently at the discretion of a woman’s doctor.

• Cervical Cancer
• Women and Cancer (book)