Hepatic arterial infusion of floxuridine and dexamethasone plus high-dose Mitomycin C for patients with unresectable hepatic metastases from colorectal carcinoma.
BACKGROUND
In vitro data suggest increased cytotoxicity with Mitomycin C (Mit-C) and Floxuridine (FUDR). Based on these data, we performed a phase II trial of hepatic arterial infusion (HAI) of FUDR and Dexamethasone (Dex) plus high-dose Mit-C for patients with unresectable hepatic metastases from colorectal carcinoma.


METHODS
High-dose Mit-C (15 mg/m2) was added via the pump sideport to HAI FUDR and Dex for 14 days of a 28-day cycle. Mit-C was given on days 1 and 29, and FUDR was given indefinitely until disease progression or discontinuation of therapy due to toxicity.


RESULTS
Sixty-three patients with unresectable liver metastases were entered. The chemotherapy-naïve group (n = 26) and those previously treated (n = 37) had similar response and median survival: 73% and 70%, and 23 and 20 months, respectively. The major toxicities were liver bilomas (7.9%), elevation in bilirubin level >3 (22%), and biliary sclerosis (9.5%). Hematologic and gastrointestinal toxicity was less than 2%.


CONCLUSIONS
The addition of high-dose Mit-C to HAI FUDR and Dex produced a high response rate even in previously treated patients. The median survival was 21 months even though half the patients were previously treated with chemotherapy. Biliary toxicity was higher than expected; therefore, alternatives to high dose Mit-C should be investigated when exploring additions to HAI therapy with FUDR and Dex.
Kemeny
Nancy
N
Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. kemenyn@mskcc.org
Eid
Ahmed
A
Stockman
Jennifer
J
Gonen
Mithat
M
Schwartz
Lawrence
L
Tetzlaff
Eric
E
Paty
Philip
P
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000473:pathology*; D003907:Dexamethasone / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage; D006499:Hepatic Artery; D006801:Humans; D015918:Infusion Pumps, Implantable; D007261:Infusions, Intra-Arterial; D007970:Leukopenia / Q000139:chemically induced; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D012004:Rectal Neoplasms / Q000473:pathology*; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced
D005467:Floxuridine; D016685:Mitomycin; D003907:Dexamethasone