Hydroxyurea may increase the activity of fluorouracil plus folinic acid in advanced gastrointestinal cancer: phase II study.
In a phase II trial, 36 patients with advanced gastrointestinal cancer were treated with: folinic acid (FA) 500 mg/m2 in a 2-hr intravenous (IV) infusion, 5- fluorouracil (5-FU) 600 mg/m2 as an IV push injection 1 hr after FA, and hydroxyurea (HU) 35 mg/kg/day given p.o. in three administrations (every 8 hr) 6 hr after 5-FU. Cycles consisted of six weekly treatments for 6 weeks, followed by a 2-week rest period. Thirty-three patients were evaluable for response and 36 for toxicity; 73% had previous chemotherapy. The response rate was 30% (CR + PR), the median duration of response was 21 weeks (range 5-36), and time to failure was 17 weeks (range 3-51). The response in patients previously exposed to chemotherapy was 29% and 44% in chemotherapy-naïve patients. The median survival for all entered patients was 28 weeks (range 6-54). The most common toxicity was gastrointestinal: diarrhea 22/36 (61%), mucositis 15/36 (42%), and nausea and vomiting 15/36 (42%); hematological toxicity was mild. We conclude that HU can potentiate the activity of 5-FU plus FA in advanced gastrointestinal cancer; in particular, HU can restore the activity of 5-FU in patients previously exposed to chemotherapy.
Di Costanzo
F
F
Medical Oncology Service, University Hospital, Terni, Italy.
el-Taani
H
H
Parriani
D
D
Tagliaventi
M
M
Bartolucci
R
R
Valenti
L
L
Manzione
L
L
Madejewicz
S
S
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D002955:Leucovorin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged
D002955:Leucovorin; D005472:Fluorouracil; D006918:Hydroxyurea