Chemoradiotherapy of Locally Advanced Esophageal Cancer

TLDR

Esophageal carcinoma has historically been treated with surgery or radiation, yet 5‑year overall survival remains only 5–10 %. This study reports the long‑term outcomes of a trial evaluating whether adding chemotherapy during radiotherapy improves survival in esophageal cancer patients. A randomized controlled trial (1985–1990) and subsequent prospective cohort (1990–1991) compared combined 50 Gy radiotherapy plus cisplatin and 5‑FU to 64 Gy radiotherapy alone in 196 patients with T1‑3 N0‑1 M0 disease across multiple institutions. Combined therapy markedly increased 5‑year overall survival to 26 % versus 0 % with radiotherapy alone, reduced disease persistence (26 % vs 37 %), but was associated with higher acute toxicity and only 68 % of patients received the planned chemotherapy.

Abstract

ContextCarcinoma of the esophagus traditionally has been treated by surgery or radiation therapy (RT), but 5-year overall survival rates have been only 5% to 10%. We previously reported results of a study conducted from January 1986 to April 1990 of combined chemotherapy and RT vs RT alone when an interim analysis revealed significant benefit for combined therapy.ObjectiveTo report the long-term outcomes of a previously reported trial designed to determine if adding chemotherapy during RT improves the survival rate of patients with esophageal carcinoma.DesignRandomized controlled trial conducted 1985 to 1990 with follow-up of at least 5 years, followed by a prospective cohort study conducted between May 1990 and April 1991.SettingMulti-institution participation, ranging from tertiary academic referral centers to general community practices.PatientsPatients had squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, adequate renal and bone marrow reserve, and a Karnofsky score of at least 50.InterventionsCombined modality therapy (n=134): 50 Gy in 25 fractions over 5 weeks, plus cisplatin intravenously on the first day of weeks 1, 5, 8, and 11, and fluorouracil, 1 g/m2 per day by continuous infusion on the first 4 days of weeks 1, 5, 8, and 11. In the randomized study, combined therapy was compared with RT only (n=62): 64 Gy in 32 fractions over 6.4 weeks.Main Outcome MeasuresOverall survival, patterns of failure, and toxic effects.ResultsCombined therapy significantly increased overall survival compared with RT alone. In the randomized part of the trial, at 5 years of follow-up the overall survival for combined therapy was 26% (95% confidence interval [CI], 15%-37%) compared with 0% following RT. In the succeeding nonrandomized part, combined therapy produced a 5-year overall survival of 14% (95% CI, 6%-23%). Persistence of disease (despite therapy) was the most common mode of treatment failure; however, it was less common in the groups receiving combined therapy (34/130 [26%]) than in the group treated with RT only (23/62 [37%]). Severe acute toxic effects also were greater in the combined therapy groups. There were no significant differences in severe late toxic effects between the groups. However, chemotherapy could be administered as planned in only 89 (68%) of 130 patients (10% had life-threatening toxic effects with combined therapy vs 2% in the RT only group).ConclusionCombined therapy increases the survival of patients who have squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, compared with RT alone.