Survival following intensive preoperative combined modality therapy with paclitaxel, cisplatin, 5-fluorouracil, and radiation in resectable esophageal carcinoma: A phase I report

Purpose: To assess the benefits of aggressive chemoradiation therapy followed by surgery in resectable esophageal carcinoma. Method: Twenty-nine patients with resectable carcinoma were treated with 60 Gy of radiation (2 Gy daily for 6 weeks) and concurrent chemotherapy consisting of continuous infusion of 5-fluorouracil (200-225 mg/m²/d), paclitaxel (25, 40, 50, or 60 mg/m²) weekly over 1 hour, and cisplatin (25 mg/m ²) weekly immediately following paclitaxel throughout radiation. Patients received either 4 cycles of postoperative paclitaxel 175 mg/m ² over 3 hours and cisplatin 75 mg/m² every 3 weeks or paclitaxel 175 mg/m² over 3 hours and cisplatin 75 mg/m² every 3 weeks prior to the initiation of chemoradiation. After induction therapy and restaging, esophagectomy was performed 4 to 6 weeks later. Results: Twenty-seven patients were eligible for study (26 men, 23 with adenocarcinoma). Median age was 58 years (range 30-73). The maximum tolerated dose combination was paclitaxel 50 mg/m² over 1 hour weekly, cisplatin 25 mg/m ² over 1 hour weekly, 5-fluorouracil 200 mg/m²/d by continuous infusion throughout radiotherapy and radiation to 60 Gy. Twenty-two patients completed therapy and underwent surgical resection. Four patients had complete pathological responses and 18 had partial responses with no mortality. The commonest dose-limiting toxicity was mucositis and esophagitis (n = 7). Median follow-up of 27 patients was 150 weeks (range 7-303). At 2-year follow-up 16/27 (59%) were alive and 15/27 (56%) were free of disease. At 4-year follow-up 12/27 (44%) were alive and free of disease. Median follow-up of 22 patients undergoing esophagectomy was 205 weeks (range 26-303). At 4-year follow-up 10/22 (45%) were alive and free of disease. For the 18 patients treated at or above the maximum tolerated dose, median follow-up was 151 weeks (range 35-206) and at 3-year follow-up 9/18 (50%) were alive and free of disease. Conclusion: Aggressive combined modality therapy of esophageal carcinoma was associated with excellent long-term survival in this phase I trial.