Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S) trial: Comparison of a sequential treatment with irinotecan (CPT-11) plus 5-fluorouracil (5-FU)/folinic acid (LV) followed by docetaxel and cisplatin versus a 5-FU/LV regimen as postoperative treatment for radically resected gastric cancer.

Abstract

LBA4001 Background: Following radical resection of gastric or gastroesophageal junction (GEJ) adenocarcinoma, a meta-analysis and randomized studies demonstrated better survival in pts treated with fluoropyrimidine regimens compared to surgery alone. ITACA-S trial is a no-profit, multicenter, randomized, open-label, superiority phase III study aimed at evaluating whether a more intensive postoperative chemotherapy improves efficacy, when replace fluoropyrimidine. Methods: Pts radically resected for gastric or GEJ adenocarcinoma, with ≥D1-lymphadenectomy, node involvement (pN+) or pN0 with pT2b-3-4; within 3-8 weeks after surgery were eligible. Treatment consisted in CPT-11 180 mg/m2 on d1, LV 100 mg/m2 d1-2, 5-FU 400-600 mg/m2 d1-2, q14; for 4 cycles (FOLFIRI regimen) followed by docetaxel 75 mg/m2 d1, cisplatin 75 mg/m2 d1, q 21; for 3 cycles (arm A) vs. LV 100 mg/m2 d1-2, 5-FU 400-600 mg/m2 d1-2, q 14 for 9 cycles (arm B). The primary hypothesis on disease-free survival (DFS) requires 636 events (first recurrence or death) to detect an hazard ratio (HR) of 0.80, with 2-sided 5% significance level for the log-rank test and a power of 80%. Results: From February 2005 to August 2009, 1,106 pts were randomized and 1,100 were analyzed (562 arm A, 538 arm B; 6 major violations) by 123 Italian centers. By March 2012, with a median follow-up of 49 months (quartile range: 36-62) we observed 558 events for DFS (HR 0.98; 95%CI 0.83-1.16;p=0.83) accounting for 88% of the target number and 440 deaths (HR: 1.00; 95%CI 0.83-1.20;p=0.98). Toxicity was consistent with literature. Given the data observed, both under the original hypothesis and the current trend, the probability to reach a statistically significant results at the target events is <0.0001. Conclusions: Adjuvant chemotherapy in gastric cancer with more intensive regimen did not result in a significant prolongation of DFS and OS when compared to bolus/infusion FU/LV regimen.