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Long-term Follow-up of a Prospective Randomized Trial (RTOG 85-01)

Jay S. Cooper, MD; Matthew D. Guo, PhD; Arnold Herskovic, MD; John S. Macdonald, MD; James A. Martenson, Jr, MD; Muhyi Al-Sarraf, MD; Roger Byhardt, MD; Anthony H. Russell, MD; Jonathan J. Beitler, MD, MBA; Sharon Spencer, MD; Sucha O. Asbell, MD; Mary V. Graham, MD; Lawrence L. Leichman, MD

JAMA. 1999;281:1623-1627.

Context  Carcinoma 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.

Objective  To 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.

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 referral 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 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 Measures  Overall survival, patterns of failure, and toxic effects.

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 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).

Conclusion  Combined therapy increases the survival of patients who have squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, compared with RT alone.

Author Affiliations: Department of Radiation Oncology, New York University, New York, NY (Dr Cooper); Radiation Therapy Oncology Group Headquarters, Philadelphia, Pa (Dr Guo); Department of Radiation Oncology, Wayne State University, Detroit, Mich (Dr Herskovic); Department of Medical Oncology, St Vincent's Cancer Center, New York, NY (Dr Macdonald); Department of Radiation Oncology, Mayo Clinic, Rochester, Minn (Dr Martenson); Department of Medical Oncology, Providence Cancer Center, Southfield, Mich (Dr Al-Sarraf); Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee (Dr Byhardt); Department of Radiation Oncology, Radiation Oncology Center, Sacramento, Calif (Dr Russell); Department of Radiation Oncology, Albert Einstein College of Medicine, New York, NY (Dr Beitler); Department of Radiation Oncology, University of Alabama, Birmingham (Dr Spencer); Department of Radiation Oncology, Albert Einstein Medical Center, Philadelphia (Dr Asbell); Department of Radiation Oncology, Washington University, St Louis, Mo (Dr Graham); and Department of Medical Oncology, Roswell Park Cancer Institute, Buffalo, NY (Dr Leichman).

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