title: Phase I-II study of 5-fluorouracil, leucovorin, doxorubicin, methotrexate, and long-term oral etoposide (FLAME) in unresectable or metastatic gastric cancer.
abstract: The objective of this phase I-II study was to determine the efficacy and toxicity of combination chemotherapy with 5-fluorouracil, leucovorin, doxorubicin, methotrexate, and oral etoposide (FLAME) in patients with measurable unresectable or metastatic gastric cancer. Starting doses on the phase I study were as follows: methotrexate 50 mg/m2 intravenous bolus day 1; leucovorin 20 mg/m2 intravenous bolus days 2 through 4, starting 24 hours after the methotrexate dose; 5-fluorouracil 325 mg/m2 intravenous bolus 15 minutes after leucovorin days 2 through 4; doxorubicin 25 mg/m2 intravenous bolus day 8; and oral etoposide 50 mg/day for 14 days, starting on day 8. A new cycle started on day 28. A total of 42 patients were treated--10 patients in the phase I study and 32 patients in the phase II study. Dose-limiting toxicity was encountered in the phase I study on the second escalation step, when doxorubicin was escalated to 30 mg/m2 and 5-fluorouracil was escalated to 350 mg/m2. In the phase II study 28 patients (109 courses) were evaluable for toxicity. Neutropenia grade 3 or more was dose limiting and was documented in 12 patients (43%) during 22 treatment courses (20%). Neutropenia was associated with febrile neutropenia requiring hospitalization in four patients during five courses of therapy. Grade 3 stomatitis and grade 3 diarrhea was infrequent, documented in two patients (two courses) and three patients (four courses), respectively. All other toxicity was grade 1 and grade 2. The combined objective response rate in 38 evaluable patients entered in both studies was 23.3% (six partial responses and one complete response). Stable disease was documented in 15 patients (39.5%). The median survival for the 42 patients entered in both trials was 6.9 months (95% confidence interval, 5.9-8.5 months). The objective response rate and median survival for the combined group is comparable with that reported for the etoposide, leucovorin, and 5-fluorouracil (ELF), and 5-fluorouracil and methotrexate (FMTX) regimens in a recently reported, multicenter, phase III study.
authors.affiliation: Toronto-Sunnybrook Regional Cancer Centre, Ontario, Canada.
authors.forename: G A
authors.initials: GA
authors.lastname: Bjarnason
authors.forename: C
authors.initials: C
authors.lastname: Cripps
authors.forename: R
authors.initials: R
authors.lastname: Goel
authors.forename: S
authors.initials: S
authors.lastname: Fine
authors.forename: A M
authors.initials: AM
authors.lastname: Oza
authors.forename: J R
authors.initials: JR
authors.lastname: Skillings
authors.forename: I
authors.initials: I
authors.lastname: Kerr
authors.forename: C J
authors.initials: CJ
authors.lastname: Germond
authors.forename: M J
authors.initials: MJ
authors.lastname: Moore
authors.forename: J A
authors.initials: JA
authors.lastname: Maroun
authors.forename: E
authors.initials: E
authors.lastname: Franssen
authors.forename: H
authors.initials: H
authors.lastname: Dulude
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis
chemical_list: D005047:Etoposide; D004317:Doxorubicin; D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate