Concurrent Chemoradiotherapy Helps Preserve Larynx

SAN FRANCISCO—In patients with potentially resectable cancer of the larynx, concurrent chemoradiotherapy cuts in half the incidence of larynx removal vs radiation therapy alone—and vs the current standard of care of induction chemotherapy followed by radiation therapy, Arlene A. Forastiere, MD, reported at the 37th Annual Meeting of the American Society of Clinical Oncology (ASCO).

"This is the new standard of care for treatment of patients with advanced larynx cancer, based on this study," said Dr. Forastiere, professor of oncology and otolaryngology, Johns Hopkins Oncology Center. She presented results of a large, randomized study (R91-11) on behalf of the Head and Neck Intergroup.

Concurrent treatment resulted in a 50% reduction in larynx removal vs radiation therapy alone, establishing concurrent chemoradiotherapy as the best nonsurgical treatment method for preserving the voice among patients with advanced larynx cancer.

"The curves plateau, such that there is a 15% chance of losing the larynx with concurrent treatment vs a 30% to 35% chance with other treatments," Dr. Forastiere said.

The Intergroup study included 547 patients with potentially resectable stage III-IV larynx cancer randomized to (1) three cycles of induction chemotherapy—cisplatin (Platinol) and 5-FU—plus radiation therapy for responders; (2) concurrent cisplatin/5-FU with radiation therapy; or (3) radiation therapy alone as the control arm. The larynx was surgically removed only in patients who did not respond. The primary endpoint was laryngectomy-free survival.

At 2 years, 68% of patients who had received concurrent chemoradiotherapy were alive with their larynx, compared with 58% for sequential chemotherapy/radiation therapy, and 53% for radiation therapy alone.

Overall larynx preservation during a patient’s lifetime, "most important in this study, for us," Dr. Forastiere said, was 88% for concurrent chemoradiotherapy, compared with 74% for chemotherapy plus radiation therapy and 69% for radiation therapy alone. Survival at 2 years (76%) did not vary among the three treatment groups.

The findings illustrate the progress made in treatment of larynx cancer in the United States over the past decade. Larynx removal was the standard of care until 10 years ago. Since 1991, induction chemotherapy has made preservation of the voice possible.

"Another way to look at it—which really shows you the change in this field over the past 10 years—is that 10 years ago, everyone lost their larynx," Dr. Forastiere said. "Now, with this treatment, only 15% of patients lose their larynx."

The discussant, Gregory T. Wolf, MD, University of Michigan Health System, said that the study added evidence that chemotherapy plus radiation therapy is better than radiation therapy alone; however, he said that the best approach to organ preservation is "yet to be defined."

He indicated that further research should look more closely at patterns of relapse and complications of concurrent chemoradiotherapy (ie, strictures, radiation necrosis, chronic edema) as well as other factors. "None of these approaches provides better survival rates than surgery," he said.

In terms of treating specific patients, Dr. Forastiere said the concurrent chemoradiotherapy regimen would be the recommended voice-preservation option for patients with advanced laryngeal cancer. However, for patients with little support at home or other significant medical problems, radiation therapy alone would be the treatment of choice.

"In all cases," she said, "patients should be followed closely during treatment by a head and neck surgeon, so that surgery can be performed if there is residual or recurrent cancer after treatment."

The synergism between radiation therapy and chemotherapy is also under study in the setting of other head and neck cancers.