The Best Treatment Approach for Locally Advanced Esophageal Cancer?

Esophageal squamous cancer is typically treated with chemoradiotherapy given as definitive treatment or prior to surgery. In Japan (where a common alternative is chemotherapy followed by surgery), investigators compared three neoadjuvant treatments in 601 patients with locally advanced esophageal squamous cancer in an open-label, randomized, multicenter trial.

The three protocols were:

• 5-day infusion of 5-FU with 1 day of cisplatin for two 3-week cycles
• That regimen plus 1 day of docetaxel, for three 3-week cycles
• 4-day infusion of 5-FU and 1 day of cisplatin for two 4-week cycles plus concurrent radiotherapy (total dose, 41.4 Gy)

The primary tumor was in the middle thoracic esophagus in 59% of patients; 68% had stage T3 disease; 91% had clinical stage II or III disease. Protocol therapy and esophagectomy were completed in similar percentages of patients across treatment arms (84%–87% and 89%–93%, respectively).

At a median follow-up of 50.7 months, the primary endpoint of 3-year overall survival (OS) was significantly superior with docetaxel triplet chemotherapy than with doublet chemotherapy (72.1% vs. 62.6%); triplet chemotherapy also showed superior 3-year progression-free survival. Pathologic complete response was higher with triplet than doublet chemotherapy (19.8% vs. 2.0%). Doublet chemotherapy plus radiotherapy had similar 3-year OS as doublet chemotherapy alone (68.3% and 62.6%, respectively) but a higher rate of pathologic complete response (38.5% vs. 2.0%). A post hoc analysis indicated a trend toward better OS with triplet chemotherapy than with chemoradiotherapy.