Chemo-biotherapy with 5-fluorouracil, leucovorin, and alpha interferon in metastatic carcinoma of the colon--a Cancer Biotherapy Research Group [CBRG] phase II study.
BACKGROUND
Biochemical modulation of 5-Fluorouracil activity with Leucovorin has been well documented in colorectal cancer. Several studies have shown increased efficacy of 5-fluorouracil in combination with alpha interferon. We therefore initiated a phase II trial of dual modulation of 5-fluorouracil with leucovorin and alpha interferon to evaluate outcomes in patients with metastatic carcinoma of the colon.


METHODS
Patients with metastatic colon carcinoma with expected survival > 4 months and performance status of ECOG < or = 2 were treated weekly with Leucovorin 400 mg i.v. followed by 5-FU 600 mg/m2 i.v. bolus. Alpha interferon 3-9 million units was administered subcutaneously every Monday, Wednesday and Friday. Patients were analyzed for toxicity, tumor response and survival.


RESULTS
Sixteen patients with a median age of 66 years were treated. Three patients were not evaluable for response but were evaluable for toxicity. Grades 3 and 4 toxicities were neutropenia, diarrhea, mucositis, nausea and vomiting, fatigue, fever, asthenia and elevated hepatic enzymes. One patient died from complications associated with diverticulitis and neutropenia. Objective response rate was 23% (95% confidence interval 4-46%) and median survival was 11.5 months (95% confidence interval 6.3-19 months). Thirty-eight percent of the patients were alive at one year and 19% at two years.


CONCLUSIONS
The combination of 5-fluorouracil, leucovorin and alpha interferon as administered in this phase II study did not result in enhanced response rate or survival. However this regimen was associated with considerable toxicity.
Soori
G S
GS
Alegent Health Bergan Mercy Cancer Center, Omaha, NE 68124, USA.
Oldham
R K
RK
Dobbs
T W
TW
Bury
M J
MJ
Church
C K
CK
DePriest
C
C
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003131:Combined Modality Therapy; D004238:Diverticulitis / Q000139:chemically induced; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D002955:Leucovorin / Q000008:administration & dosage; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D016019:Survival Analysis; D017211:Treatment Failure
D007155:Immunologic Factors; D016898:Interferon-alpha; D002955:Leucovorin; D005472:Fluorouracil