Concurrent Chemo/RT More Likely to Save Larynx

NEW ORLEANS—In stage III and low-volume stage IV laryngeal cancer, concurrent chemotherapy and radiotherapy was superior to two other approaches in controlling tumor and preserving the larynx, according to a three-arm Intergroup trial presented at the 44th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (abstract plenary 4). Moshe H. Maor, MD, of the Radiation Oncology Department, M.D. Anderson Cancer Center, presented the results.

"Our findings demonstrate that concurrent chemotherapy and radiation treatment is superior to chemotherapy followed by radiation and radiation alone when attempting to preserve a patient’s larynx," Dr. Maor said. "We can now offer patients an excellent therapy that can spare them from the lifelong effects of a total laryngectomy."

The study, RTOG 91-11, included 547 patients (517 analyzed) with a new diagnosis of a potentially resectable stage III or IV squamous carcinoma of the glottic or supraglottic region; those with a T1 or a high-volume T4 tumor were excluded from the study. Patients were randomly assigned to three treatment arms:

n Arm 1 (control): Three cycles of induction cisplatin (Platinol) 100 mg/m2 once and fluorouracil 1,000 mg/m²/d for 5 days every 3 weeks. Responding patients then received 70 Gy of radiation in 35 fractions for 49 days.

n Arm 2: Concurrent cisplatin 100mg/m² on days 1, 22, and 43 of radiotherapy with 70 Gy in 35 fractions for 49 days.

n Arm 3: Radiation only with 70 Gy in 35 fractions for 49 days.

Patients with a neck node 3 cm or greater or with multiple neck nodes underwent a neck dissection 8 weeks after completion of therapy.

At 2 years, the laryngeal preservation rate was significantly greater for patients treated with concomitant chemotherapy/radiotherapy, compared with the other two treatment arms. The number of laryngectomies was 43 of 173 patients (25.3%) in the induction chemotherapy group, 21 of 172 (12.2%) in the concomitant therapy group, and 52 of 172 (30.5%) in the radiation-only group.

Locoregional failure was significantly less common in the concomitant therapy arm, occurring in 38.6%, 21.5%, and 44.3% of arms 1, 2, and 3, respectively. The difference between induction and concurrent chemotherapy was statistically significant, but there was no difference between induction chemotherapy and radiotherapy alone. Distant metastases occurred in 15.1%, 11.8%, and 21.9%, of arms 1, 2, and 3, respectively, with a significant difference favoring concomitant chemoradiation over radiotherapy alone (P = .03). The salvage rate was high (about 75%) in all three arms.

The only difference in laryngectomy-free survival was between the two experimental arms; there were no differences between induction chemotherapy and either concurrent chemoradiation or radiotherapy alone.

"When we compared experimental concomitant therapy with control induction, larynx preservation and locoregional control were superior in the concomitant arm. But there was no difference in laryngectomy-free survival between the two arms, due to the greater number of unrelated deaths in the concomitant arm (36 vs 19 patients)," Dr. Maor said.

Acute grade 3-4 toxicities were seen in 78%, 79%, and 59% of arms 1, 2, and 3, respectively. Ten patients died from treatment-related toxicity: 5 in the induction chemotherapy arm and 5 in the concomitant chemoradiation arm.

"The take-home message is that when chemotherapy with radiation is indicated in laryngeal cancer, it should be given concurrently. Where salvage is not an option, concurrent therapy may improve survival, compared with sequential chemotherapy," Dr. Maor said.

Discussion

Louis Harrison, MD, chairman of radiation oncology, Beth Israel and St. Luke’s-Roosevelt Medical Center, New York, called RTOG 91-11 a "very important study that sets a new standard of larynx preservation." He said that continued focus on maximizing both oncologic outcomes and quality-of-life outcomes like larynx preservation "is a model for all oncology." He added, however, that "we must continue to develop organ preservation treatment programs and tailor treatment intensity to specific anatomical sites."

The focus should be on treatment intensification for many head and neck cancers, such as pyriform sinus cancer and hypopharynx cancer, in order to preserve the larynx, he said. On the other hand, he noted, not all head and neck cancers warrant intensive treatment. In particular, patients with oropharynx cancers tend to achieve good results with radiotherapy alone and should undergo chemotherapy only under certain situations. The same can be said for base of the tongue cancer, which responds well to radiotherapy alone. "We need to add chemotherapy selectively in these patients," Dr. Harrison said.

While organ preservation is highly justified, there is also a need to identify better selection criteria for patients "doomed to failure, who may be better served by laryngectomy and other types of reconstruction," he added.

Dr. Harrison said that concomitant chemotherapy and radiotherapy "represents the next logical step" in the management of head and neck cancers, and he predicted continuing progress. Functional imaging modalities now detect recurrent or persistent disease earlier. Also, better radiotherapy fractionation and new agents in the pipeline, such as tyrosine kinase inhibitors, may enhance treatment response in the future, he concluded.