Gemcitabine (GEM) plus oxaliplatin, folinic acid, and 5-fluorouracil (FOLFOX-4) in patients with advanced gastric cancer.
OBJECTIVE
oxaliplatin in combination with folinic acid (FA) and infusional 5-fluorouracil (5-FU) has shown significant anti-tumor activity in gastric cancer patients (FOLFOX). Previous studies have shown that gemcitabine (GEM), a new fluorinated anti-metabolite, enhances the individual anti-tumor activity of either 5-FU or oxaliplatin. We have therefore designed a multi-center phase II trial in order to test a novel GEM+FOLFOX-4 regimen in patients with metastatic gastric cancer.


METHODS
we enrolled 36 patients, 28 males and 8 females, with an average age of 64.4 years (range 37-78), who received bi-weekly treatment with GEM (1,000 mg/m2 on day 1), levo-FA (100 mg/m2 on days 1 and 2), a 5-FU (400 mg/m2) bolus injection followed by 22-h continuous infusion (800 mg/m2) on days 1 and 2, and oxaliplatin 85 mg/m2 in a 4-6 h intravenous (i.v.) infusion before the second FUFA administration on day 2.


RESULTS
the most frequent side effect was grade 1-2 hematological toxicity and late sensorial neurotoxicity. Two patients developed hypersensitivity to oxaliplatin while another developed an aseptic eosinophilic pneumonitis. Two patients refused to continue the treatment after two cycles of chemotherapy and were lost at the follow-up. Among the remaining 34 patients four achieved a complete response, 15 a partial response, 12 had a stable disease and three progressed.


CONCLUSIONS
these results may grant the rationale to evaluate this multi-drug combination in randomized phase III trials in advanced gastric cancer.
Correale
Pierpaolo
P
Section of Medical Oncology, Human Pathology and Oncology Department, Siena University School of Medicine, Viale Bracci 11, 53100, Siena, Italy. correale@unisi.it
Fulfaro
Fabio
F
Marsili
Stefania
S
Cicero
Giuseppe
G
Bajardi
Eugenia
E
Intrivici
Chiara
C
Vuolo
Giuseppe
G
Carli
Antonio Ferdinando
AF
Caraglia
Michele
M
Del Prete
Salvatore
S
Greco
Ettore
E
Gebbia
Nicola
N
Francini
Guido
G
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000473:pathology; D006402:Hematologic Diseases / Q000139:chemically induced / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D009944:Organoplatinum Compounds; D003841:Deoxycytidine; D002955:Leucovorin; D005472:Fluorouracil; D000093542:Gemcitabine