The VA study was followed up in a randomized study, RTOG-91-11 (NCT00002496), in which the laryngeal preservation arm of the VA study was compared with the concomitant chemoradiation and radiation-alone arms, and the primary endpoint was laryngectomy-free survival (LFS). The RTOG 91-11 study evaluated 547 patients with locally advanced laryngeal cancer who were enrolled between August 1992 and May 2000, with a median follow-up for surviving patients of 10.8 years (range, 0.07-17 years). Three regimens were compared, including induction chemotherapy plus radiation therapy, concomitant chemoradiation, and radiation therapy alone. Both chemotherapy regimens improved LFS compared with radiation therapy alone (induction chemotherapy vs. radiation therapy alone, hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.59-0.95; P = .02; concomitant chemotherapy vs. radiation therapy alone, HR, 0.78; 95% CI, 0.78-0.98; P = .03).
Concurrent radiation therapy plus cisplatin resulted in a statistically significantly higher percentage of patients with an intact larynx at 10 years (67.5% for patients who had induction chemotherapy; 81.7% for patients who had concomitant chemotherapy; and 63.8% for patients who received radiation alone); 80% of laryngectomies were performed during the first 2 years (84 laryngectomies during year 1 and 35 laryngectomies during year 2).
Concomitant cisplatin with radiation therapy resulted in a 41% reduction in risk of locoregional failure compared with radiation therapy alone (HR, 0.59; 95% CI, 0.43-0.82; P = .0015) and a 34% reduction in risk compared with induction chemotherapy (HR, 0.66; 95% CI, 0.48-0.92; P = .004). Both chemotherapy regimens had a lower incidence of distant metastases, although this did not reach statistical significance compared with radiation therapy alone.
The 10-year cumulative rates of late toxicity (grades 3-5) were 30.6% for induction chemotherapy, 33.3% for concomitant chemotherapy, and 38% for radiation alone, and were not significantly different between the arms.
OS was not significantly different between the groups, although there was possibly a worse outcome in the concomitant groups compared with the induction chemotherapy group (HR, 1.25; 95% CI, 0.98-1.61; P = .08). The OS rates were 58% (5 year) and 39% (10 year) for induction chemotherapy, 55% (5 year) and 28% (10 year) for concomitant chemoradiation, and 54% (5 year) and 32% (10 year) for radiation alone. The number of deaths not attributed to larynx cancer or treatment were higher with concomitant chemotherapy (30.8% vs. 20.8% with induction chemotherapy and 16.9% with radiation alone), because after approximately 4.5 years, the survival curves began to separate and favor induction, although the difference was not statistically significant.