Multimodal treatment for squamous cell carcinoma of the esophagus: results with two different strategies

Abstract

The prognosis of patients with esophageal cancer treated with esophagectomy alone is disappointing. To improve these results, the addition of chemotherapy and/or radiotherapy to surgery has been proposed. Since 1992, we have enrolled patients with locally-advanced squamous-cell esophageal carcinoma in two successive studies to evaluate the feasibility and efficacy of preoperative chemotherapy and concomitant chemotherapy plus radiotherapy.Between 1992 and 1994, 29 patients were treated with three courses of cisplatin 100 mg/m2 on day 1, fluorouracil (5-Fu) (750 mg/m2/day) by continuous infusion days 1 through 5, and folinic acid (200 mg/m2/day) days 1 to 5. Cycles were repeated every 3 weeks. Since November 1996, 21 patients have been included in a 3-week intensive schedule with weekly cisplatin (30 mg/m2 on days 1, 8 and 15) and continuous infusion of 5-Fu (300 mg/m2, days 1 to 21) plus concurrent hyperfractionated radiotherapy (1.5 Gy twice daily, total dose of 45 Gy, for 3 weeks). In both studies, patients underwent esophagectomy 3 to 5 weeks after induction therapy.In the preoperative chemotherapy scheme, a clinical response was observed in 30% of patients and one patient had a pathological complete response (pCR). The resectability rate was 58%, and five patients (17%) died in the postoperative period. Median survival and 3-year survival rate were 10 months and 4%, respectively. In the chemoradiotherapy study, a clinical response was observed in 19 (90%) of patients. A complete resection was performed in 15 patients (71%) and 7 patients (43% of all resected tumors) had a pCR. There have been no treatment-related deaths. To date, the median survival and 3-year survival rate are 27 months and 41%, respectively. In the chemotherapy study, the most frequent acute high-grade (3 or 4) toxicities were mucositis, observed in 44% of cycles, while severe, esophagitis was detected in 66% of patients treated with chemoradiotherapy.In our experience, preoperative chemotherapy does not seems to improve the results obtained with esophagectomy alone; furthermore, this approach was related to a significant postoperative mortality. On the contrary, concomitant chemotherapy with hyperfractionated radiotherapy has demonstrated a high activity with an encouraging 3-year survival rate. In spite a high incidence of esophagitis, this schedule is feasible without increasing postoperatory risk.