Phase I-II trial of weekly gemcitabine plus high-dose 5-fluorouracil and leucovorin in advanced pancreatic cancer.
BACKGROUND
Pancreatic cancer is a dismal disease. Few drugs, including gemcitabine and 5-fluorouracil (5-FU), have notable antitumor effects against advanced pancreatic cancer. The purpose of the present study was to determine the maximum tolerated dose (MTD) of 5-FU and the efficacy and toxicity profile of weekly gemcitabine plus infusional 5-FU/leucovorin in advanced pancreatic cancer.


METHODS
Patients with histo-/cytologically confirmed, advanced pancreatic cancer were eligible. Treatment consisted of a 30-min infusion of gemcitabine (800 mg/m2), followed by a 24-h infusion of 5-FU and leucovorin (300 mg/m2) at day 1, day 8 and day 15 every 28 days, and was termed the GemFL24 regimen. The dose of 5-FU was escalated from 1600, 2000, to 2600 mg/m2 in the phase I study, and fixed MTD for subsequent enrolled patients.


RESULTS
Eighteen patients were enrolled in the phase I study, and 24 in phase II. The MTD of 5-FU was 2000 mg/m2, with major dose-limiting toxicities being febrile neutropenia and delayed recovery from neutropenia. The dose intensity of gemcitabine of the 35 patients with 5-FU dosage set at MTD was 593 mg/m2 per week. In the entire series of 42 patients, myelosuppression was the main toxicity, with grade 3 neutropenia in eight patients, and grade 3/4 thrombocytopenia in six. On an intention-to-treat analysis, the overall and clinical benefit response rates were 22% and 46%, respectively; with median progression-free and overall survival of 4.1 and 6.9 months, respectively.


CONCLUSIONS
The GemFL24 regimen is a feasible and moderately active treatment with manageable toxicities for advanced pancreatic cancer, and could be a basis for further combination with other anticancer drugs.
Shiah
Her-Shyong
HS
Division of Cancer Research, National Health Research Institutes, Veterans General Hospital, Taipei, Taiwan.
Cheng
Ann-Lii
AL
Hsu
Chiun
C
Hsu
Chih-Hung
CH
Liu
Tsang-Wu
TW
Chang
Jang-Yang
JY
Jan
Chang-Ming
CM
Chao
Yee
Y
Yu
Wei-Lan
WL
Chuang
Tsai-Rong
TR
Whang-Peng
Jacqueline
J
Chen
Li-Tzong
LT
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D002955:Leucovorin; D005472:Fluorouracil; D000093542:Gemcitabine