Bimonthly high dose leucovorin and 5-fluorouracil 48-hour infusion with interferon-alpha-2a in patients with advanced colorectal carcinoma. Groupe d'Etude et de Recherche sur les Cancers de l'Ovaire et Digestifs (GERCOD).
BACKGROUND; The rationale for the modulation of 5-fluorouracil (5-FU) with interferon-alpha (IFN) is inhibition of 5-FU catabolism and 5-FU resistance. Clinical trials have shown debatable results when IFN is given in high doses with 5-FU used as a bolus alone or in combination with leucovorin (LV). A first-line Phase II study was performed in 50 patients with metastatic colorectal carcinoma who were given a bimonthly combination of high dose LV, a high dose 48-hour infusion of 5-FU, and a low dose of IFN.


METHODS
The regimen was comprised of a 2-hour infusion of LV, 500 mg/m2, on each of 2 consecutive days, and a 48-hour infusion of 5-FU, 1.5 to 2 g/m2/24 hours, starting after Day 1 of LV treatment every 2 weeks until there was evidence of disease progression. IFN was administered subcutaneously three times weekly at a dose of 3 MU (body surface area [BSA] < 1.75 m2) or 4.5 MU (BSA > OR = 1.75 m2).


RESULTS
World Health Organization toxicity Grade 3-4 occurred in 21 patients (42%): diarrhea in 6%, mucositis in 12%, neutropenia in 30%, and alopecia in 8%. The overall response rate was 44%; 1 patient had a complete response (2%), 21 had partial responses (42%), 23 had stable disease (46%), and 5 had disease progression (10%). The median progression free survival was 9 months, and median survival was 25 months.


CONCLUSIONS
Bimonthly high dose LV, a high dose 48-hour infusion of 5-FU, and a low dose of IFN had good activity in patients with advanced colorectal carcinoma. However, as in other schedules of LV and 5-FU, IFN induces high grade toxicity.
Tournigand
C
C
Hôpital Saint-Antoine, Paris, France.
Louvet
C
C
de Gramont
A
A
Lucchi
E
E
Seitz
J F
JF
Mal
F
F
Raymond
E
E
Cady
J
J
Carola
E
E
Krulik
M
M
D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D016019:Survival Analysis
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002955:Leucovorin; D005472:Fluorouracil