C. Louvet et al., Phase II trial of bimonthly leucovorin, 5-fluorouracil and gemcitabine foradvanced pancreatic adenocarcinoma (FOLFUGEM), ANN ONCOL, 12(5), 2001, pp. 675-679
Background: Gemcitabine alone or 5-fluorouracil (5-FU) according to several
schedules are used for palliation of metastatic and locally advanced (LA)
pancreatic adenocarcinoma. This study was designed to test the efficacy of
the leucovorin-5-FU and gemcitabine combination.
Patients and methods: This phase II trial combined a simplified bimonthly L
V5FU2 with gemcitabine: leucovorin 400 mg/m(2) in a two-hour infusion, foll
owed by 5-fluorouracil 400 mg/m(2) bolus and 2 or 3 g/m(2) continuous infus
ion over 46 hours; gemcitabine 1 g/m(2) was infused over 30 min on day 3 af
ter 5-FU. Treatment was repeated every two weeks. Gemcitabine dose could be
increased (250 mg/m(2) every two cycles up to 1500 mg/m(2)) in the absence
of NCI-CTC toxicity >2.
Results: Among the 62 patients included in this study, 22 had LA and 40 had
metastatic disease. Objective response rate for the 54 patients with measu
rable disease was 25.9% (95% confidence interval (CI): 14%-37.8%) and 22.6%
(95% CI: 12%-33.2%) in the intent-to-treat population; the clinical benefi
t rate for the 59 assessable patients was 49.2%. Median progression-free su
rvival and median overall survival were 4.8 and 9 months, respectively, wit
h 32.3% of patients alive at 1 year. The most frequent toxicity (grade 3-4)
was neutropenia (56.5%) usually asymptomatic (1.1% febrile neutropenia), b
ut requiring decreases of 5-FU and gemcitabine doses. Unexpected complete a
lopecia occurred in 97% of patients.
Conclusions: Palliative effects, response rate and survival observed in thi
s multicenter study seem to be superior to those obtained with gemcitabine
or 5-FU alone, despite a limiting hematological toxicity.