Adjuvant Chemoradiotherapy With Epirubicin, Cisplatin, and Fluorouracil Compared With Adjuvant Chemoradiotherapy With Fluorouracil and Leucovorin After Curative Resection of Gastric Cancer: Results From CALGB 80101 (Alliance)

Abstract

Purpose After curative resection of gastric or gastroesophageal junction adenocarcinoma, Intergroup Trial 0116 (Phase III trial of postoperative adjuvant radiochemotherapy for high risk gastric and gastroesophageal junction adenocarcinoma: Demonstrated superior survival for patients who received postoperative chemoradiotherapy with bolus fluorouracil (FU) and leucovorin (LV) compared with surgery alone. CALGB 80101 (Alliance; Phase III Intergroup Trial of Adjuvant Chemoradiation After Resection of Gastric or Gastroesophageal Adenocarcinoma) assessed whether a postoperative chemoradiotherapy regimen that replaced FU plus LV with a potentially more active systemic therapy could further improve overall survival. Patients and Methods Between April 2002 and May 2009, 546 patients who had undergone a curative resection of stage IB through IV (M0) gastric or gastroesophageal junction adenocarcinoma were randomly assigned to receive either postoperative FU plus LV before and after combined FU and radiotherapy (FU plus LV arm) or postoperative epirubicin, cisplatin, and infusional FU (ECF) before and after combined FU and radiotherapy (ECF arm). Results With a median follow-up duration of 6.5 years, 5-year overall survival rates were 44% in the FU plus LV arm and 44% in the ECF arm ( P_logrank = .69; multivariable hazard ratio, 0.98; 95% CI, 0.78 to 1.24 comparing ECF with FU plus LV). Five-year disease-free survival rates were 39% in the FU plus LV arm and 37% in the ECF arm ( P_logrank = .94; multivariable hazard ratio, 0.96; 95% CI, 0.77 to 1.20). In post hoc analyses, the effect of treatment seemed to be similar across all examined patient subgroups. Conclusion After a curative resection of gastric or gastroesophageal junction adenocarcinoma, postoperative chemoradiotherapy using a multiagent regimen of ECF before and after radiotherapy does not improve survival compared with standard FU and LV before and after radiotherapy.

Fig 1.

Flow diagram of all registered patients. ECF, epirubicin, cisplatin, and fluorouracil; FU, fluorouracil; LV, leucovorin.

Fig 2.

(A) Overall survival by treatment arm. (B) Disease-free survival by treatment arm. ECF, epirubicin, cisplatin, and fluorouracil; FU, fluorouracil; LV, leucovorin.

Fig 3.

Forest plot of hazard ratios and 95% CIs for overall survival by variable stratum. Numbers of events were too small to estimate the hazard ratios for other race, 0 positive nodes, and proximal gastric primary site. Box size reflects the precision of the estimate, with a larger box size indicating greater precision. ECF, epirubicin, cisplatin, and fluorouracil; FU, fluorouracil; GE, gastroesophageal; LV, leucovorin; NOS, not otherwise specified ; PS, performance status; Q, Quartile.

Fig A1.

(A) Cumulative incidence plot for locoregional versus distal recurrence among all patients. Recurrence is measured from study entry until documented recurrence of disease or last follow-up. (B) Cumulative incidence plot for locoregional versus distal recurrence by treatment assignment. Recurrence was measured from study entry until documented recurrence of disease or last follow-up. ECF, epirubicin, cisplatin, and fluorouracil; FU, fluorouracil; LV, leucovorin.