PREOPERATIVE AND POSTOPERATIVE COMBINATION CHEMOTHERAPY FOR POTENTIALLY RESECTABLE GASTRIC-CARCINOMA

Background: Median survival of patients with local-regional gastric ca rcinoma is 10 months. Resection of the primary tumor and regional lymp h nodes, with tumor-free margins (curative resection), has been the mo st effective treatment for local-regional gastric carcinoma. However, median survival of patients with curative resection of gastric carcino ma is 24 months, and the 5-year survival rate is about 20%. A single i nstitution pilot study has established the feasibility of administerin g two courses of chemotherapy preoperatively and three courses postope ratively. In another study, a 15% pathologically documented complete r esponse (pathologic complete response) has been reported in unresectab le gastric carcinoma treated with etoposide, doxorubicin, and cisplati n. Purpose: Our purpose was to increase the curative resection rate in potentially resectable gastric carcinoma and to delay or eliminate mi crometastases and thus improve survival. We also evaluated clinical an d pathologic response to chemotherapy. Methods: Forty-eight previously untreated patients with potentially resectable gastric carcinoma rece ived a chemotherapy regimen (EAP) consisting of etoposide (120 mg/m2 i ntravenously over a 2-hour period on days 4, 5, and 6), doxorubicin (2 0 mg/m2 as a 10-minute intravenous infusion on days 1 and 7), and cisp latin (40 mg/m2 as a 1-hour intravenous infusion on days 2 and 8). Pat ients received three courses of chemotherapy before resection, and res ponding patients received two courses postoperatively. Clinical and pa thologic response rates, toxicity, patterns of treatment failure, and survival times were assessed. Results: A median of three courses (rang e, 1-5) of preoperative therapy was administered; six (12%) of the 48 patients had clinical complete response, and nine (19%) had partial re sponse. Forty-one (85%) underwent surgery; 37 (90%) of these 41 (77% o f the 48 patients) had a curative resection. There were no pathologic complete responses. Median survival for all patients is 15.5 months (r ange, 2-29+ months). Therapy was discontinued because of the toxic eff ects in one patient before surgery and in six patients after surgery. Doses were reduced in 37 patients (77%), mainly because of hematologic toxicity. Nineteen (40%) were hospitalized because of toxic effects, including 15 patients who developed fever with neutropenia. Grade 3 or 4 nausea and vomiting occurred in 15 patients and grade 3 or 4 diarrh ea in seven patients. One death was directly related to chemotherapy. Conclusions: These data support that administration of preoperative an d postoperative chemotherapy for local-regional gastric carcinoma is f easible in a multi-institutional setting. Our findings demonstrate tha t this EAP regimen is modestly active but is associated with substanti al toxicity. Implications: Use of preoperative chemotherapy in resecta ble gastric carcinoma merits further evaluation, but more effective dr ug regimens will be required before a controlled trial is initiated.