Randomised phase II evaluation of irinotecan plus high-dose 5-fluorouracil and leucovorin (ILF) vs 5-fluorouracil, leucovorin, and etoposide (ELF) in untreated metastatic gastric cancer

Abstract

An open-label randomised comparison of efficacy and tolerability of irinotecan plus high-dose 5-fluorouracil (5-FU) and leucovorin (LV) (ILF) with etoposide plus 5-FU/LV (ELF) in patients with untreated metastatic or locally advanced gastric cancer. One cycle of ILF comprised six once-weekly infusions of irinotecan 80 mg m À2 , LV 500 mg m À2 , 24-h 5-FU 2000 mg m À2 , and ELF comprised three once-daily doses of etoposide 120 mg m À2 , LV 300 mg m À2 , 5-FU 500 mg m À2 . In all, 56 patients received ILF and 58 ELF. Median age was 62 years, Karnofsky performance 90%, and disease status was comparable for both arms. The objective clinical response rates after 14 weeks treatment (primary end point) were 30% for ILF and 17% for ELF (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.29 -1.13, P ¼ 0.0766). Overall response rates over the entire treatment period for ILF and ELF were 43 and 24%, respectively (RR 0.56, 95% CI 0.33 -0.97; P ¼ 0.0467). For ILF and ELF, respectively, median progression-free survival was 4.5 vs 2.3 months, time to treatment failure was 3.6 vs 2.2 months (P ¼ 0.4542), and overall survival was 10.8 vs 8.3 months (P ¼ 0.2818). Both regimens were well tolerated, the main grade 3/4 toxicities being diarrhoea (18%, ILF) and neutropenia (57%, ELF). The data from this randomised phase II study indicate that ILF provides a better response rate than ELF, and that ILF should be investigated further for the treatment of metastatic gastric cancer.

ERCC1 mRNA levels and survival of advanced gastric cancer patients treated with a modified FOLFOX regimen

“…Irinotecan and taxane-based regimens have been used in the treatment of advanced gastric cancer patients, with survival times similar to those attained with FOLFOX (Moehler et al, 2005;Oh et al, 2007;Takayama et al, 2007). However, the short survival attained in FOLFOX-treated patients with positive protein ERCC1 (HR, 1.91) (Kwon et al, 2007) or overexpression of ERCC1 mRNA (HR, 9.4) suggests that irinotecan or taxane-based regimens could be the better alternative for these patients.…”

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].…”

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).…”