Aggressive multimodality therapy for stage III esophageal cancer: a phase I/II study.
BACKGROUND
Stage III advanced locoregional esophageal carcinoma is frequently unresectable and inconsistently represented in therapeutic trials of esophageal cancer.


METHODS
From 1992 to 1998, 34 of 131 total esophageal cancer patients were designated stage III (16 T3N1, 9 T4N0, 9 T4N1) and medically fit to enter a combined modality protocol with continuous infusion 5-fluorouracil (CIS-FU, 300 to 600 mg/m2/day), high-dose external beam irradiation (60 Gy), and interval esophagectomy. Staging before and after induction therapy included computed tomography; endoscopy, and endoscopic ultrasound.


RESULTS
Significant toxicity from induction therapy included death (5/34; 14.7%), pneumonitis (5/34; 14.7%), mucositis (13/34; 38%), and hand-foot syndrome (3/34; 8.8%). In addition to the five deaths, 11 patients did not proceed to operation because of development of esophagorespiratory fistula in 3, distant disease in 2, persistence of T4 stage in 2, progression of comorbidities in 2, and patient refusal in 2. There was a discrepancy between clinical complete response (cCR) at restaging 56% (19/34) and pathologic CR (pCR) noted at the time of operation (8/34; 23.5%). Complete resections were possible in 16 of 18 patients explored. Complications in 4 patients included: death (1), airway injury (1), chylothorax requiring reoperation (1), anastomotic leak (1), recurrent nerve injury with vocal cord paresis (2), and ascaris infection (1). Actuarial survival analysis using the Kaplan-Meier method and log-rank testing showed a 36-month survival of 20% for the group as a whole and 27% for patients restaged cCR (cCR vs PR, p = 0.0046). Treatment failure is predominantly distant, with good local control in resected patients. N0 node status was strongly associated with survival (N0 vs N1 p = 0.0024). There is a trend towards improved survival in the resected group (resected 22% vs nonresected 10% at 3 years, p = 0.17).


CONCLUSIONS
Response rates and survival are commensurate with multiple completed phase II and III trials. These are attained at a higher treatment-related mortality. T4 patients can be successfully resected in selected patients. Even in advanced disease, nodal status is a significant predictor of survival.
Alexander
E P
EP
Division of Cardiothoracic Surgery, Washington, DC VAMC, USA. epalexander@med.va.gov
Lipman
T
T
Harmon
J
J
Wadleigh
R
R
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016629:Esophagectomy; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil