A phase I study of gemcitabine and uracil-ftorfar (UFT)/leucovorin.
BACKGROUND
Gemcitabine and uracil-ftorfar (UFT) are nucleotide analogs with overlapping clinical activity and complementary mechanisms of action. The primary objective of this study was to determine the maximum tolerated dose of UFT/leucovorin and gemcitabine.


METHODS
The major eligibility criteria included a diagnosis of nonhematologic cancer with no conventional effective therapy, normal organ function, and Eastern Cooperative Oncology Group performance status of 0-2. The starting doses were 600 mg/m2 gemcitabine weekly for 3 of 4 weeks and 150 mg/m2 UFT daily and 30 mg leucovorin 3 times a day, both for 21 days. Cycles were repeated every 28 days.


RESULTS
Twenty-eight patients (male:female 13:15) were treated. The median number of cycles per patient was 3 (range, 0-17). Two of 3 patients on dose level 4 (250 mg/m2 UFT, 800 mg/m2 gemcitabine) developed dose-limiting toxicities consisting of hand-foot syndrome and infection.


CONCLUSIONS
The recommended doses for phase II trials are 800 mg/m2 gemcitabine days 1, 8, and 15 and 200 mg/m2 UFT per day and 90 mg leucovorin per day on days 1 through 21.
El-Rayes
Basil F
BF
Division of Hematology and Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, USA. elrayesb@karmanos.org
Zalupski
Mark
M
Shields
Anthony F
AF
Manza
Stephanie G
SG
LoRusso
Patricia
P
Philip
Philip A
PA
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D005641:Tegafur / Q000008:administration & dosage; D014498:Uracil / Q000008:administration & dosage; D000093542:Gemcitabine
D003841:Deoxycytidine; D005641:Tegafur; D014498:Uracil; D002955:Leucovorin; D000093542:Gemcitabine