Phase I-II study of 5-fluorouracil, leucovorin, doxorubicin, methotrexate,and long-term oral etoposide (FLAME) in unresectable or metastatic gastriccancer

The objective of this phase I-II study was to determine the efficacy and to xicity of combination chemotherapy with 5-fluorouracil, leucovorin, doxorub icin, methotrexate, and oral etoposide (FLAME) in patients with measurable unresectable or metastatic gastric cancer. Starting doses on the phase I st udy were as follows: methotrexate 50 mg/m(2) intravenous bolus day 1; leuco vorin 20 mg/m(2) intravenous bolus days 2 through 4, starting 24 hours afte r the methotrexate dose; 5-fluorouracil 325 mg/m(2) intravenous bolus 15 mi nutes after leucovorin days 2 through 4; doxorubicin 25 mg/m(2) 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 patie nts in the phase I study and 32 patients in the phase II study. Dose-limiti ng toxicity was encountered in the phase I study on the second escalation s tep, when doxorubicin was escalated to 30 mg/m(2) and 5-fluorouracil was es calated to 350 mg/m(2). In the phase II study 28 patients (109 courses) wer e evaluable for toxicity. Neutropenia grade 3 or more was dose limiting and was documented in 12 patients (43%) during 22 treatment courses (20%). Neu tropenia was associated with febrile neutropenia requiring hospitalization in four patients during five courses of therapy. Grade 3 stomatitis and gra de 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% co nfidence interval, 5.9-8.5 months). The objective response rate and median survival for the combined group is comparable with that reported for the et oposide, leucovorin, and 5-fluorouracil (ELF), and 5-fluorouracil and metho trexate (FMTX) regimens in a recently reported, multicenter, phase III stud y.