Hepatic arterial floxuridine and leucovorin for unresectable liver metastases from colorectal carcinoma. New dose schedules and survival update.
BACKGROUND
We studied three new dose schedules of hepatic arterial infusion of floxuridine (FUDR) and leucovorin and update survival analysis of a previously reported trial using these drugs by hepatic arterial infusion for patients with hepatic metastases from colorectal carcinoma.


METHODS
Untreated patients with hepatic metastases from colorectal cancer were treated with three dose schedules: Group D, FUDR (0.3 mg/kg/day) and leucovorin (30 mg/m2/day) as a 14-day continuous infusion through an implantable hepatic arterial pump alternating with a 4-week rest period; Group E, a lower dose of FUDR (0.25 mg/kg/day) and leucovorin (30 mg/m2/day) as a 14-day infusion alternating with 2 weeks of saline; and Group F, FUDR (0.3 mg/kg/day) with a lower leucovorin dose (15 mg/m2/day) for 2 weeks followed by a 2-week rest.


RESULTS
In 42 patients with unresectable hepatic metastases, the complete-plus-partial response rate was 56%, with a median survival of 24.2 months. Complete-plus-partial response rates for groups D, E, and F were 30%, 54%, and 75%, respectively. Twelve percent of the 42 patients developed biliary sclerosis; the percentages of patients per group were 17%, 15%, and 6%, respectively. Updated median survival of the original 24 patients treated with FUDR and leucovorin by hepatic arterial infusion and these 42 new patients (66 total) was 28.8 months. One-, two-, three-, four-, and five-year survival rates were 86%, 62%, 31%, 15%, and 7%, respectively.


CONCLUSIONS
Hepatic arterial chemotherapy with FUDR and leucovorin for patients with hepatic metastases from colorectal carcinoma yields a high response rate and 1- and 2-year survivals of 86% and 62%, respectively. Although a lower dose of leucovorin (15 mg/m2) with FUDR produces a high response rate with less toxicity, before larger scale trials are initiated, further investigation is needed to reduce toxicity. A study of hepatic arterial dexamethasone with FUDR and leucovorin has been initiated for this purpose.
Kemeny
N
N
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Seiter
K
K
Conti
J A
JA
Cohen
A
A
Bertino
J R
JR
Sigurdson
E R
ER
Botet
J
J
Chapman
D
D
Mazumdar
M
M
Budd
A J
AJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000556:secondary*; D015179:Colorectal Neoplasms / Q000473:pathology*; D004334:Drug Administration Schedule; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage* / Q000627:therapeutic use; D006499:Hepatic Artery; D006801:Humans; D015918:Infusion Pumps, Implantable; D007261:Infusions, Intra-Arterial; D002955:Leucovorin / Q000008:administration & dosage* / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis
D005467:Floxuridine; D002955:Leucovorin