Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781.
OBJECTIVE
The primary treatment modality for patients with carcinoma of the esophagus or gastroesophageal junction has been surgery, although primary radiation therapy with concurrent chemotherapy produces similar results. As both have curative potential, there has been great interest in the use of trimodality therapy. To this end, we compared survival, response, and patterns of failure of trimodality therapy to esophagectomy alone in patients with nonmetastatic esophageal cancer.


METHODS
Four hundred seventy-five eligible patients were planned for enrollment. Patients were randomly assigned to either esophagectomy with node dissection alone or cisplatin 100 mg/m(2) and fluorouracil 1,000 mg/m(2)/d for 4 days on weeks 1 and 5 concurrent with radiation therapy (50.4 Gy total: 1.8 Gy/fraction over 5.6 weeks) followed by esophagectomy with node dissection.


RESULTS
Fifty-six patients were enrolled between October 1997 and March 2000, when the trial was closed due to poor accrual. Thirty patients were randomly assigned to trimodality therapy and 26 were assigned to surgery alone. Patient and tumor characteristics were similar between groups. Treatment was generally well tolerated. Median follow-up was 6 years. An intent-to-treat analysis showed a median survival of 4.48 v 1.79 years in favor of trimodality therapy (exact stratified log-rank, P = .002). Five-year survival was 39% (95% CI, 21% to 57%) v 16% (95% CI, 5% to 33%) in favor of trimodality therapy.


CONCLUSIONS
The results from this trial reflect a long-term survival advantage with the use of chemoradiotherapy followed by surgery in the treatment of esophageal cancer, and support trimodality therapy as a standard of care for patients with this disease.
Tepper
Joel
J
Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7512, USA. tepper@med.unc.edu
Krasna
Mark J
MJ
Niedzwiecki
Donna
D
Hollis
Donna
D
Reed
Carolyn E
CE
Goldberg
Richard
R
Kiel
Krystyna
K
Willett
Christopher
C
Sugarbaker
David
D
Mayer
Robert
R
D000230:Adenocarcinoma / Q000628:therapy; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000628:therapy; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D016629:Esophagectomy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome
D002945:Cisplatin; D005472:Fluorouracil