Preoperative and Postoperative Combination Chemotherapy for Potentially Resectable Gastric Carcinoma

• Published in: JNCI : Journal of the National Cancer Institute 1993-11, Vol.85 (22), p.1839-1844
• Main Authors: Ajani, Jaffer A., Mayer, Robert J., Ota, David M., Steele, Glenn D., Evans, Douglas, Roh, Mark, Sugarbaker, David J., Dumas, Pamela, Gray, Catherine, Vena, Donald A., Stablein, Donald M.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Adenocarcinoma - surgery; Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cancer; Chemotherapy; Chemotherapy, Adjuvant; Cisplatin - administration & dosage; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Digestive system; Doxorubicin - administration & dosage; Etoposide - administration & dosage; Female; Humans; Male; Medical research; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Stomach Neoplasms - surgery; Survival Analysis; Time Factors; Treatment Failure
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/85.22.1839

Background: Median survival of patients with local-regional gastric carcinoma is 10 months. Resection of the primary tumor and regional lymph nodes, with tumor-free margins (curative resection), has been the most effective treatment for local- regional gastric carcinoma. However, median survival of patients with curative resection of gastric carcinoma is 24 months, and the 5-year survival rate is about 20%. A single institution pilot study has established the feasibility of administering two courses of chemotherapy preoperatively and three courses postoperatively. In another study, a 15% pathologically documented complete response (pathologic complete response) has been reported in unresectable gastric carcinoma treated with etoposide, doxorubicin, and cisplatin. Purpose: Our purpose was to increase the curative resection rate in potentially resectable gastric carcinoma and to delay or eliminate micrometastases and thus improve survival. We also evaluated clinical and pathologic response to chemotherapy. Methods: Forty-eight previously untreated patients with potentially resectable gastric carcinoma received a chemotherapy regimen (EAP) consisting of etoposide (120 mg/m2 intravenously over a 2-hour period on days 4, 5, and 6), doxorubicin (20 mg/m2 as a 10-minute intravenous infusion on days 1 and 7), and cisplatin (40 mg/m2 as a 1-hour intravenous infusion on days 2 and 8). Patients received three courses of chemotherapy before resection, and responding patients received two courses postoperatively. Clinical and pathologic response rates, toxicity, patterns of treatment failure, and survival times were assessed. Results: A median of three courses (range, 1-5) of preoperative therapy was administered; six (12%) of the 48 patients had clinical complete response, and nine (19%) had partial response. Forty-one (85%) underwent surgery; 37 (90%) of these 41 (77% of the 48 patients) had a curative resection. There were no pathologic complete responses. Median survival for all patients is 15.5 months (range, 2–29+ months). Therapy was discontinued because of the toxic effects 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 diarrhea in seven patients. One death was directly rela