title: 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(-2), LV 500 mg m(-2), 24-h 5-FU 2000 mg m(-2), and ELF comprised three once-daily doses of etoposide 120 mg m(-2), LV 300 mg m(-2), 5-FU 500 mg m(-2). 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 = 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 = 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 = 0.4542), and overall survival was 10.8 vs 8.3 months (P = 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.
authors.affiliation: Klinikum der Johannes-Gutenberg-Universität, Mainz, Dortmund, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Moehler
authors.forename: A
authors.initials: A
authors.lastname: Eimermacher
authors.forename: J
authors.initials: J
authors.lastname: Siebler
authors.forename: T
authors.initials: T
authors.lastname: Höhler
authors.forename: A
authors.initials: A
authors.lastname: Wein
authors.forename: M
authors.initials: M
authors.lastname: Menges
authors.forename: D
authors.initials: D
authors.lastname: Flieger
authors.forename: T
authors.initials: T
authors.lastname: Junginger
authors.forename: T
authors.initials: T
authors.lastname: Geer
authors.forename: E
authors.initials: E
authors.lastname: Gracien
authors.forename: P R
authors.initials: PR
authors.lastname: Galle
authors.forename: M
authors.initials: M
authors.lastname: Heike
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D004943:Esophagogastric Junction; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D058766:Levoleucovorin; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D000077146:Irinotecan; D058766:Levoleucovorin; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin