Intensive preoperative chemotherapy with colony-stimulating factor for resectable adenocarcinoma of the esophagus or gastroesophageal junction.
OBJECTIVE
The curative resection rate in patients with potentially resectable carcinoma of the esophagus is approximately 55% and their median survival time is 11 months. Preoperative chemotherapy with high doses of chemotherapeutic agents was used to evaluate clinical and pathologic responses, curative resection rate, toxicity, and survival. Colony-stimulating factor (CSF) was added to reduce the severity of myelosuppression.


METHODS
Twenty-six consecutive assessable patients with potentially resectable adenocarcinoma of the esophagus or gastroesophageal junction were treated with two preoperative courses of intensive chemotherapy (etoposide, doxorubicin, and cisplatin [EAP]) with granulocyte-macrophage CSF (GM-CSF). Additional three conventional-dose postoperative chemotherapy courses without GM-CSF were given to patients who responded to preoperative chemotherapy.


RESULTS
A median of three courses (range, one to six), were administered. Of 27 patients, 26 were assessable for response to preoperative EAP; 13 (50%) achieved a major response. Among 23 patients who underwent surgery, 15 (65%) had a curative resection (58% of 26 assessable patients); none of the patients had a pathologic complete response, but two patients had only microscopic carcinoma in the resected specimen. Six patients had carcinoma present at the resection margins and received postoperative radiotherapy. Two patients were found to have liver metastases at exploration. At a median follow-up of 22 months, the median survival of 26 patients was 12.5 months (range, 2 to 32 +). Fourteen patients died of their carcinoma; two patients died of treatment-related causes; one died of an unrelated CNS arterial malformation; and the causes of death in two patients remain unknown. Seven patients are alive with no evidence of relapse. Major toxicities of this regimen included severe myelosuppression, nausea and vomiting, infections, and severe constitutional symptoms related to GM-CSF. However, subcutaneous injection of GM-CSF was well tolerated.


CONCLUSIONS
High-dose EAP is active against locoregional adenocarcinoma of the esophagus and gastroesophageal junction but can be associated with significant toxicity. Although this strategy remains attractive and needs to be developed further, less toxic and more effective regimens need to be identified.
Ajani
J A
JA
Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030-4095.
Roth
J A
JA
Ryan
M B
MB
Putnam
J B
JB
Pazdur
R
R
Levin
B
B
Gutterman
J U
JU
McMurtrey
M
M
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000517:prevention & control*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000601:surgery; D004943:Esophagogastric Junction / Q000601:surgery; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome
D005047:Etoposide; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002945:Cisplatin