Integration of surgery in multimodality therapy for esophageal cancer

While adding chemotherapy to radiation for the treatment of esophageal cancers has been shown to be beneficial, surgery usually follows treatment or is omitted. In either case, regional control remains problematic. The purpose of this study was to test the feasibility of using chemotherapy and radiation following surgery in the treatment of of esophageal cancer and to assess the impact of this approach on regional control and survival.

Twenty-five patients with esophageal cancer were treated in a phase I pilot protocol consisting of initial esophagectomy with gastroesophagostomy and subsequent combined chemotherapy and radiation. Chemotherapy consisted of cisplatin given on day 1 and 5-fluorouracil (FU) on days 1-5 by continuous infusion. Radiation therapy was administered in varying fractionation schedules of once or twice daily concomitantly with the chemotherapy. Treatment was repeated every other week for two to four cycles. Median follow-up was 42 months.

Acute toxicities (mucositis and cytopenias) were common but not worse than grade 3. Higher doses of 50 Gy with 2 Gy b.i.d. hyperfractionation caused late complications in four of 10 patients, (two lethal). Control of local disease for all patients was excellent with only two known and two possible local recurrences (16%) but distant metastases were common (46%). Disease-free survival was 58 and 30% at 1 and 2 years, respectively. Survival was 58 and 32% at 1 and 2 years, respectively (median survival, 19 months).

The local control rate and survival were better than those in our historical experience with cisplatin and 5-FU chemotherapy and radiation given prior to surgery. A dose-fractionation schedule of < 2 Gy up to a total of 50 Gy b.i.d. is recommended to avoid late adverse effects. The role of surgery will be defined by randomized studies. Better systemic therapy is needed to impact on systemic failure.