Combined therapy improves survival for advanced head and neck cancer

April 13, 2000

Intensive treatment combining radiation and chemotherapy can control locally advanced head and neck cancer, improve survival, and in most cases eliminate the need for debilitating surgery, report researchers from the University of Chicago Medical Center and Northwestern University in the April 14, 2000, issue of the Journal of Clinical Oncology.

Combined therapy provided complete local control for 92 percent of patients, most of whom had stage-IV disease, and increased long-term survival (measured at three years) to 55 percent. Only seven percent of patients required traditional surgery at the site of the primary cancer.

"We were able to produce an exceedingly high local control rate, avoid surgery and dramatically improve patient survival," said study director Everett Vokes, MD, professor of medicine and section chief of hematology/oncology at the University of Chicago. "But those gains came at a cost of frequent and severe side effects."

"Fortunately," added Vokes, "this study has pointed us toward new ways to improve survival and reduce the toxicities."

The researchers treated 76 patients between 1993 and 1996 with intensive therapy for advanced cancers of the head and neck. Treatment involved three anti-cancer drugs--cisplatin, fluorouracil and hydroxyurea--and twice-a-day radiation therapy directed at the tumor bed for five days, followed by nine days of rest. This two-week cycle was repeated five times. (Cisplatin was given only every other cycle.)

Intensive local therapy was followed by up to a year of less intense systemic treatment with cis-retinoic acid (a derivative of vitamin A) and interferon in an effort to control any microscopic tumors that had spread to distant sites from the initial cancer.

Most head and neck cancers--which include cancer of the sinuses, mouth, tongue, pharynx, larynx, and upper esophagus--grow rapidly and invade nearby tissues but are slow to spread to distant sites. Consequently, most patients with advanced disease have died from a local recurrence of their tumor, even after aggressive treatment.

Traditional therapy involved mutilating and debilitating surgery followed by radiation treatments. More recently, oncologists have used chemotherapy and radiation instead of surgery to try to preserve affected organs, such as the tongue and larynx. But recurrence of the original tumor has remained the major cause of treatment failure.

"This study is the first to reverse the historical pattern of failure," said Vokes. Fewer than 10 percent of patients had a local recurrence after treatment, but 20 percent of patients had their disease resurface at a distant site. "This means we now have to shift our attention to systemic therapy and find better ways to prevent distant metastases," said Vokes."

Unfortunately, most patients had severe short-term side effects, which include mouth pain, swallowing problems, and bone marrow damage resulting in decreased immunity and blood clotting. About 80 percent had serious decreases in their white blood cells, which protect against infection, or in their platelets, which control blood clotting. Despite intensive supportive care, four patients died during treatment from infections that took advantage of their decreased immune function.

The side effects went away after treatment, however. When surveyed one year after therapy, most patients said their physical well being--including speech and swallowing--and quality of life had returned.

The researchers are now testing new ways to decrease these side effects, including substituting paclitaxel (Taxol), which causes fewer side effects, for the highly toxic cisplatin.

"This study demonstrates that we can eliminate many of these cancers but that we still have problems with the way we go about it," concluded Vokes. "We need to find ways to make therapy easier on the patient and better methods to prevent distant spread. But this study proves that we can control local disease, usually without surgery."

Also contributing to this research were Ralph Weichselbaum, Daniel Haraf, Eileen Dolan, Laura Sulzen, Marcy List, Mary Ellyn Witt, Rob Hummerickhouse and Kirsten Stenson from the University of Chicago, and Merrill Kies, Harold Pelzer, Yi-Ching Hsieh, and Bharat Mittal from Northwestern.

The research was supported by the National Institutes of Health; the Geraldi-Norton Memorial Corporation of Northfield, Illinois; Amgen of Thousand Oaks, California; and the Duchossois family.

Summary:
Intensive treatment combining radiation and chemotherapy can control locally advanced head and neck cancer, improve survival and in most cases eliminate the need for debilitating surgery. Combined therapy provided complete local control for 92 percent of patients with advanced disease. --JCO: April, 2000, Vol. 18, #8, pp1652-1661--