Phase I study of biweekly gemcitabine followed by oxaliplatin and simplified 48-h infusion of fluorouracil/leucovorin for advanced pancreatic cancer.
OBJECTIVE
To evaluate the feasibility and maximal tolerated dose (MTD) of oxaliplatin of a triplet regimen consisting of gemcitabine, oxaliplatin and infusional fluorouracil (5-FU)/leucovorin (LV) (GOFL) for advanced pancreatic cancer.


METHODS
Patients with histologically proven metastatic or unresectable, locally advanced pancreatic adenocarcinoma were eligible to take part in the study. The treatment consisted of fixed-rate infusion (10 mg/m2/minute) of 800 mg/m2 gemcitabine followed by 2-h infusion of oxaliplatin and then 48-h infusion of 5-FU/LV day 1 and day 15 every 4 weeks. The oxaliplatin would be evaluated at three dose levels, 65, 75 and 85 mg/m2.


RESULTS
A total of 15 patients were enrolled at three dose levels. Dose-limiting toxicity of neutropenic fever and grade 4 thrombocytopenia occurred in one of each six patients at oxaliplatin dose level of 65 mg/m2 and 85 mg/m2, respectively. The MTD of oxaliplatin for this combination was 85 mg/m2. After a median four cycles of treatment, grade 3/4 neutropenia occurred in 46.7% of patients and thrombocytopenia in 13.3%. Non-hematological toxicities were generally of grade 1/2. Objective tumor response was observed in five patients (33.3%, 95% confidence interval, 6.3-60.4%).


CONCLUSIONS
Biweekly GOFL is a feasible regimen for advanced pancreatic cancer. For further phase II studies, the recommended dose of oxaliplatin is 85 mg/m2.
Ch'ang
Hui-Ju
HJ
Division of Cancer Research, National Health Research Institutes, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Wang
Chuan-Cheng
CC
Cheng
Ann-Lii
AL
Hsu
Chiun
C
Lu
Yen-Shen
YS
Chang
Ming-Chu
MC
Lin
Jaw-Town
JT
Wang
Hsiu-Po
HP
Shiah
Her-Shyong
HS
Liu
Tsang-Wu
TW
Chang
Jang-Yang
JY
Whang-Peng
Jacqueline
J
Chen
Li-Tzong
LT
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D014803:Vitamin B Complex / Q000008:administration & dosage; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D014803:Vitamin B Complex; D002955:Leucovorin; D005472:Fluorouracil; D000093542:Gemcitabine