Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiation Therapy

The Department of Veterans Affairs (VA) Laryngeal Cancer Study Group directly compared chemotherapy followed by radiation therapy versus up-front surgery with postoperative radiation therapy. A total of 332 patients were randomly assigned to either three cycles of chemotherapy (cisplatin and 5-FU) and radiation therapy or surgery and radiation therapy.[12]

The Department of Veterans Affairs (VA) Laryngeal Cancer Study Group directly compared chemotherapy followed by radiation therapy versus up-front surgery with postoperative radiation therapy. A total of 332 patients were randomly assigned to either three cycles of chemotherapy (cisplatin and 5-FU) and radiation therapy or surgery and radiation therapy.[12]

After two cycles of chemotherapy, the clinical tumor response was complete in 31% of the patients, and there was a partial response in 54% of the patients. Survival was similar in both arms; however, larynx preservation was possible in 64% of the patients in the chemotherapy-followed-by-radiation therapy arm.

The VA study was followed by a randomized study, RTOG 9111 (NCT00002496), in which the laryngeal preservation arm of the VA study was compared with the concurrent chemoradiation therapy and radiation therapy-alone arms. The primary end point was laryngectomy-free survival.[4] RTOG 9111 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 neoadjuvant chemotherapy plus radiation therapy, concurrent chemoradiation therapy, and radiation therapy alone.

The VA study was followed by a randomized study, RTOG 9111 (NCT00002496), in which the laryngeal preservation arm of the VA study was compared with the concurrent chemoradiation therapy and radiation therapy-alone arms. The primary end point was laryngectomy-free survival.[4] RTOG 9111 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 neoadjuvant chemotherapy plus radiation therapy, concurrent chemoradiation therapy, and radiation therapy alone.

Both chemotherapy regimens improved laryngectomy-free survival compared with radiation therapy alone (neoadjuvant chemotherapy vs. radiation therapy alone, HR, 0.75; 95% confidence interval [CI], 0.59–0.95; P = .02; concurrent chemotherapy vs. radiation therapy alone, HR, 0.78; 95% CI, 0.78–0.98; P = .03).

The VA study was followed by a randomized study, RTOG 9111 (NCT00002496), in which the laryngeal preservation arm of the VA study was compared with the concurrent chemoradiation therapy and radiation therapy-alone arms. The primary end point was laryngectomy-free survival.[4] RTOG 9111 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 neoadjuvant chemotherapy plus radiation therapy, concurrent chemoradiation therapy, and radiation therapy alone.

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 neoadjuvant chemotherapy; 81.7% for patients who had concurrent chemotherapy; and 63.8% for patients who received radiation therapy alone); 80% of laryngectomies were performed during the first 2 years (84 laryngectomies during year 1 and 35 laryngectomies during year 2).

The VA study was followed by a randomized study, RTOG 9111 (NCT00002496), in which the laryngeal preservation arm of the VA study was compared with the concurrent chemoradiation therapy and radiation therapy-alone arms. The primary end point was laryngectomy-free survival.[4] RTOG 9111 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 neoadjuvant chemotherapy plus radiation therapy, concurrent chemoradiation therapy, and radiation therapy alone.

Concurrent 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 neoadjuvant 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 VA study was followed by a randomized study, RTOG 9111 (NCT00002496), in which the laryngeal preservation arm of the VA study was compared with the concurrent chemoradiation therapy and radiation therapy-alone arms. The primary end point was laryngectomy-free survival.[4] RTOG 9111 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 neoadjuvant chemotherapy plus radiation therapy, concurrent chemoradiation therapy, and radiation therapy alone.

The 10-year cumulative rates of late toxicity (grades 3–5) were 30.6% for neoadjuvant chemotherapy, 33.3% for concurrent chemotherapy, and 38% for radiation therapy alone, and were not significantly different between the arms.

The VA study was followed by a randomized study, RTOG 9111 (NCT00002496), in which the laryngeal preservation arm of the VA study was compared with the concurrent chemoradiation therapy and radiation therapy-alone arms. The primary end point was laryngectomy-free survival.[4] RTOG 9111 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 neoadjuvant chemotherapy plus radiation therapy, concurrent chemoradiation therapy, and radiation therapy alone.

OS was not significantly different between the groups, although there was possibly a worse outcome in the concurrent groups compared with the neoadjuvant 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 neoadjuvant chemotherapy, 55% (5 year) and 28% (10 year) for concurrent chemoradiation therapy, and 54% (5 year) and 32% (10 year) for radiation therapy alone.

The VA study was followed by a randomized study, RTOG 9111 (NCT00002496), in which the laryngeal preservation arm of the VA study was compared with the concurrent chemoradiation therapy and radiation therapy-alone arms. The primary end point was laryngectomy-free survival.[4] RTOG 9111 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 neoadjuvant chemotherapy plus radiation therapy, concurrent chemoradiation therapy, and radiation therapy alone.

The number of deaths not attributed to larynx cancer or treatment were higher with concurrent chemotherapy (30.8% vs. 20.8% with neoadjuvant chemotherapy and 16.9% with radiation alone), because after approximately 4.5 years, the survival curves began to separate and favor neoadjuvant chemotherapy, although the difference was not statistically significant.