Does perioperative chemotherapy improve survival in patients undergoing surgery for gastroesophageal cancer?

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Abstract

BACKGROUND

The chemotherapy regimen epirubicin, cisplatin and infused fluorouracil (ECF) improves survival in patients with incurable gastric adenocarcinoma.

OBJECTIVE

To determine whether ECF administered before and after radical surgery could improve outcome over surgery alone in patients with potentially curable gastric cancer.

DESIGN

Patients of any age were eligible if they had histologically proven adenocarcinoma of the esophagogastric junction, lower third of the esophagus or stomach, but no evidence of distant metastases or locally advanced inoperable disease. Patients who had poor performance status, prior cytotoxic chemotherapy or radiotherapy, renal disease or uncontrolled cardiac disease were excluded.

INTERVENTION

Between July 1994 and April 2002, patients were randomly assigned to radical total or subtotal gastrectomy alone or accompanied by three preoperative and three postoperative cycles of chemotherapy. The extent of lymph-node dissection was decided by the surgeon. Each 3-week cycle of chemotherapy comprised intravenous epirubicin (50 mg/m2) and cisplatin (60 mg/m2) on day 1, and continuous intravenous infusion of fluorouracil (200 mg/m2) daily for 21 days. Dose modification was permitted in response to treatment-related toxicity.

OUTCOME MEASURES

The primary endpoint of the study was overall survival; secondary endpoints were progression-free survival, pathological and surgical assessments of down-staging, surgeon's assessment of results of surgery, and quality of life.

RESULTS

Median follow-up was 47-49 months. Compared with patients who underwent surgery alone, patients who received perioperative chemotherapy had markedly improved progression-free survival (hazard ratio for progression 0.66, 95% CI 0.53-0.81; P<0.001) and overall survival (hazard ratio for death 0.75, 95% CI 0.60-0.93; P = 0.009). Survival rates after 5 years were 36.3% (95% CI 29.5-43%) in the perioperative chemotherapy group, and 23% (95% CI 16.6-29.4%) in the surgery group. Rates of postoperative complications and the number of deaths by 30 days after surgery were similar in both groups. Resection was curative in 69.3% of the perioperative chemotherapy group and 66.4% of the surgery group. Resected tumors were smaller in the perioperative chemotherapy group than in the surgery group (diameter 3 cm vs 5 cm; P<0.001). Among all patients undergoing resection, there was a greater proportion of stage T1 and T2 tumors in the perioperative chemotherapy group than in the surgery group (51.7% vs 36.8%; P = 0.002). Over a median follow-up of 4 years, 149 patients in the group receiving perioperative chemotherapy and 170 patients in the group receiving surgery alone died. Only 104 of 250 patients assigned to perioperative chemotherapy completed all six cycles; reasons for not completing chemotherapy varied, but patient choice was an important factor.

CONCLUSION

A perioperative regimen of ECF down-staged tumors and improved progression-free survival and overall survival in patients with operable gastric or lower esophageal adenocarcinoma.

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