Dual modulation of 5-fluorouracil with folinic acid and hydroxyurea in metastatic colorectal cancer.
Leucovorin and 5-fluorouracil (5-FU) can be further modulated with hydroxyurea. Sixty-eight patients with advanced colorectal cancer received every 2 weeks hydroxyurea per os 1.5 g to 2 g days -1, 1, and 2; leucovorin 200 mg/m2 iv over 2 hours started at least 1 hour after hydroxyurea and per os 100 mg/m2 12 hours later, on days 1 and 2; 5-FU, bolus 400 mg/m2 during leucovorin infusion and 24 hours continuous infusion 600 mg/m2, repeated on days 1 and 2. Two complete responses (7%), 8 partial responses (30%), 12 no change (44%), and 5 progressions (19%) were observed among 31 nonpreviously treated patients. Four partial response (11%), 15 no change (43%), and 16 progressions (46%) were observed among 37 pretreated patients. Nineteen were treated after progression on the same regimen without oral leucovorin and hydroxyurea, 1 achieved PR and 10 showed no change. Among them, 6 experienced response or stabilization of longer duration than with previous treatment. Twelve-month survival was 61% in non-pretreated and 43% in pretreated patients as of the start of chemotherapy. Toxicity was mild with nausea in 46%, diarrhea in 37%, and mucositis in 36%. The first-line response rate is in the range of leucovorin and 5-FU alone. Some pretreated patients benefited from this regimen.
de Gramont
A
A
Service de Médecine Interne-Oncologie, Hôpital Saint-Antoine, Paris, France.
Louvet
C
C
Bennamoun
M
M
Varette
C
C
Demuynck
B
B
Beerblock
K
K
Moreau
S
S
Soubrane
D
D
Mal
F
F
Grangé
J D
JD
Zylberait
D
D
Krulik
M
M
D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged
D002955:Leucovorin; D005472:Fluorouracil; D006918:Hydroxyurea