Chemoradiotherapy of locally advanced esophageal cancer - Long-term follow-up of a prospective randomized trial (RTOG 85-01)

Context Carcinoma of the esophagus traditionally has been treated by surger y or radiation therapy (RT), but 5-year overall survival rates have been on ly 5% to 10%, We previously reported results of a study conducted from Janu ary 1986 to April 1990 of combined chemotherapy and RT vs RT alone when an interim analysis revealed significant benefit for combined therapy. Objective To report the long-term outcomes of a previously reported trial d esigned to determine if adding chemotherapy during RT improves the survival rate of patients with esophageal carcinoma. Design Randomized 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. Setting Multi-institution participation, ranging from tertiary academic ref erral centers to general community practices. Patients Patients 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. Interventions Combined modality therapy (n = 134). 50 Gy in 25 fractions ov er 5 weeks, plus cisplatin intravenously on the first day of weeks 1, 5, 8, and 11, and fluorouracil, 1 g/m(2) per day by continuous infusion on the f irst 4 days of weeks 1, 5, 8, and 1 1, In the randomized study, combined th erapy was compared with RT only (n = 62): 64 Gy in 32 fractions over 6.4 we eks. Main Outcome Measures Overall survival, patterns of failure, and toxic effe cts. Results Combined 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 nonrandomi zed part, combined therapy produced a 5-year overall survival of 14% (95% C I, 6%-23%). Persistence of disease (despite therapy) was the most common mo de of treatment failure; however, it was less common in the groups receivin g combined therapy (34/130 [26%]) than in the group treated with RT only (2 3/62 [37%]). Severe acute toxic effects also were greater in the combined t herapy groups. There were no significant differences in severe fate toxic e ffects between the groups. However, chemotherapy could be administered as p lanned in only 89 (68%) of 130 patients (10% had life-threatening toxic eff ects with combined therapy vs 2% in the RT only group). Conclusion Combined therapy increases the survival of patients who have squ amous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, compared with RT alone.