Intensive chemoradiation followed by esophagectomy for squamous cell and adenocarcinoma of the esophagus.
OBJECTIVE
To determine the pathologic complete response rate, toxicity, and survival of patients with resectable squamous cell or adenocarcinoma of the esophagus treated with a 30-day preoperative chemoradiation regimen and surgical resection.


METHODS
Fifty patients (16 squamous, 33 adeno, one undifferentiated) who had carcinoma of the esophagus (limited to the primary tumor and regional or celiac nodes) were treated with cisplatin 26 mg/m2/day continuous infusion days 1 through 5 and 26 through 30, 5-fluorouracil (5-FU) 300 mg/m2/day continuous infusion days 1 through 30, and radiation 44 Gy, 2 Gy/fx in 22 daily fractions, days 1 through 30, followed by esophagectomy.


RESULTS
Forty-seven patients underwent esophagectomy (94% operability rate), and 45 had total gross removal of disease and negative margins of resection (90% resectability rate). Nineteen patients (40%) had a pathologic complete response (CR). Forty (80%) received 100% of the planned cisplatin dose, 29 (58%) received 100% of the planned 5-FU dose, and 40 (80%) received > or = 80% of the planned 5-FU dose. Forty-five (90%) received the planned 44-Gy radiation dose. Grade 3 or 4 neutropenia occurred in 60% of patients. The incidence of febrile neutropenia was 34%. There was one septic death during chemoradiation and no operative deaths. Weight loss requiring nutritional support occurred in 50% of patients, secondary to anorexia, dysphagia, and/or esophagitis. The survival of all registered patients at a median follow-up of 43 months was 2-year survival 58%, median 31.3 months. Survival analysis by histology showed no difference between the two histologic types (squamous vs adenocarcinoma). However, survival by pathologic response was significantly different: pathologic CR, 19 patients, 2-year survival 78%, median survival 58 months; and pathology positive, 28 patients, 2-year survival 46%, median survival 22.4 months. A Cox proportional hazards model and logistic regression analysis demonstrated a significant survival advantage for pathologic CRs and stage I disease versus higher-stage disease and a correlation between chemotherapy dose received and pathologic staging.


CONCLUSIONS
This 30-day chemoradiation regimen followed by surgery resulted in a high pathologic complete response rate, 40%, and apparent survival advantage for this group. The median survival rate of 31.3 months and 2-year survival rate of 58% suggest that this regimen may improve survival over surgical treatment alone. Randomized trials with large accrual and statistical power are necessary to confirm our results and to determine optimal treatment.
Forastiere
A A
AA
Department of Oncology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Heitmiller
R F
RF
Lee
D J
DJ
Zahurak
M
M
Abrams
R
R
Kleinberg
L
L
Watkins
S
S
Yeo
C J
CJ
Lillemoe
K D
KD
Sitzmann
J V
JV
Sharfman
W
W
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D016629:Esophagectomy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced