Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction

Abstract

IF did not yield a significant TTP or OS superiority over CF, and the results of noninferiority of IF were borderline. However, IF may provide a viable, platinum-free front-line treatment alternative for metastatic gastric cancer.

Optimal chemotherapy for advanced gastric cancer: is there a global consensus?

“…The first phase II study results suggested that irinotecan and 5-fluorouracil combinations had promising antitumoral activity and efficacy [49,50]. A randomized controlled phase III trial failed to show the superiority of irinotecan and high-dose 5-fluorouracil over only cisplatin and 5-fluorouracil [51]. However, quality of life tended to be better during treatment with irinotecan and 5-fluorouracil.…”

Phase II study of sequential cisplatin plus 5-fluorouracil/leucovorin (5-FU/LV) followed by irinotecan plus 5-FU/LV followed by docetaxel plus 5-FU/LV in patients with metastatic gastric or gastro-oesophageal junction adenocarcinoma

“…Three randomized trials tested treatment combinations of infused 5-FU and irinotecan [7,17,18]. A phase III trial randomized 333 patients to irinotecan plus high-dose 5-FU and leucovorin (IF) or cisplatin and 5-FU (CF).…”

“…The IF regimen was not superior over CF for time to progression (5.0 versus 4.2 months), median OS time 9.0 versus 8.7 months, or RR 31.8% versus 25.8%, but showed a better safety profile: in fact, while increased rate of grade 3-4 diarrhoea was reported with IF, the incidence of grade 3-4 stomatitis and haematological toxicity, in particular neutropenic fever, was significantly lower. [7]. According to a meta-analysis, irinotecan regimens show a non-statistically significant benefit in survival of about 1 month and a lower rate of treatment-related deaths over the reference regimen [3].…”

“…A recent phase III randomized trial compared the combination of irinotecan plus 5-FU (IF) to cisplatin plus 5-FU [7], demonstrating that IF was not inferior to the standard doublet in terms of time to progression (TTP) in the full-analysis population and resulted in a different toxicity profiles compared to cisplatin-based treatment, thus representing a possible platinum-free alternative in the first-line treatment of advanced gastric cancer (AGC).…”

Oxaliplatin, irinotecan, and fluorouracil/folinic acid in advanced gastric cancer: a multicenter phase II trial of the Southern Italy Cooperative Oncology Group

“…The IFF regimen produced a greater response rate (RR) (32 vs. 25%), and demonstrated a marginally signiWcant superior progression-free survival (PFS) (5.0 vs. 4.2 months, P = 0.088), but not overall survival (OS) (9.0 vs. 8.7 months) in comparison with the reference regimen, showing a better toxicity proWle [14].…”