A three-step strategy of induction chemotherapy then chemoradiation followed by surgery in patients with potentially resectable carcinoma of the esophagus or gastroesophageal junction

BACKGROUND. Patients with locoregional carcinoma of the esophagus or gastroesophageal junction have a poor survival rate after surgery. Preoperative chemotherapy or chemoradiotherapy has not improved the outcome for these patients. Our study was designed to assess the feasibility of preoperative induction combination chemotherapy in addition to chemoradiotherapy to improve the curative resection rate, local control, and survival. PATIENTS AND METHODS. Patients having histologic proof of localized carcinoma (either squamous cell carcinoma or adenocarcinoma) of the esophagus or gastroesophageal junction underwent full classification including endoscopic ultrasonography (EUS). Patients first received up to two courses of induction chemotherapy consisting of 5-fluorouracil at 750 mg/m²/day as continuous infusion on Days 1-5, cisplatin at 15 mg/m²/day as an intravenous bolus on Days 1-5, and paclitaxel at 200 mg/m² as a 24-hour intravenous infusion on Day 1. The second course was repeated on Day 29. This was followed by radiotherapy (45 grays in 25 fractions) and concurrent admission of 5-fluorouracil (300 mg/m²/day as a continuous infusion 5 days/week) and cisplatin (20 mg/m² on Days 1-5 of radiotherapy). After chemoradiotherapy, patients underwent surgery. The feasibility of this approach, curative resection rates, patient survival, and patterns of failure were assessed. RESULTS. Thirty-seven of 38 patients enrolled were evaluable for toxicity and survival. Adenocarcinoma and distal esophageal location of carcinoma were observed frequently. Thirty-five (95%) of the 37 patients underwent surgery, all of whom had an R0 (curative) resection. A pathologic complete response was noted in 11 (30%) of the 37 total patients. In addition, 5 patients (14%) had only microscopic carcinoma. According to EUS classification, 31 (89%) of the 35 patients who underwent surgery had a T3 carcinoma whereas according to pathologic classification only 3 (9%) had a T3 carcinoma (P ≤ 0.01). Similarly, according to EUS classification, 23 patients (66%) had an N1 carcinoma, whereas according to pathologic classification only 7 patients (20%) had an N1 carcinoma (P ≤ 0.01). At a median follow-up of 20 months (minimum follow-up, 13+ months; maximum follow-up, 36+ months), the median survival duration for the 37 patients had not yet been reached. In addition, there were two deaths related to surgery. CONCLUSIONS. These data show that the three-step strategy of preoperative paclitaxel-based induction chemotherapy then chemoradiotherapy followed by surgery is feasible and appears quite active in patients having locoregional carcinoma of the esophagus or gastroesophageal junction. Future investigations should focus on substituting cisplatin with less toxic agents and including more systemic therapy with newer classes of agents.