Treatment of hepatic-metastatic colorectal cancer with a chemotherapeutic emulsion: interim results of a phase I trial.
BACKGROUND
Hepatic arterial infusion of 5-fluoro-2-deoxyuridine (FUdR) is associated with a 60% response rate among previously untreated patients who have hepatic-metastatic colorectal cancer. One obstacle to further dose escalation has been concomitant hepatic toxicity. We are evaluating a FUdR-containing chemotherapeutic emulsion to further dose intensify therapy without associated toxicity.


METHODS
The in vitro pharmacokinetics of the emulsion were determined using high-pressure liquid chromatography (HPLC). The rate at which FUdR is released from emulsion into an overlying aqueous phase was determined in static and dynamic assays. Fifteen patients with hepatic-metastatic colorectal cancer were treated with intrahepatic arterial infusions of emulsion on a phase I dose-escalating clinical protocol. Serum collection determined systemic drug levels using HPLC.


RESULTS
In vitro studies demonstrate that FUdR is slowly released from emulsion into overlying aqueous medium. The emulsion serves as a depot for FUdR. Therapy was well tolerated. Emulsion was sequestered in the liver after infusion in all treated patients.


CONCLUSIONS
This Ethiodol-based, oil-in-water emulsion serves as a sustained-release preparation of FUdR. An Ethiodol-based oil-in-water emulsion is a clinically effective vehicle for delivering FUdR to hepatic-metastatic colorectal tumors.
Rubin
J T
JT
Department of Surgery, University of Pittsburgh Medical Center, PA 15213, USA.
Lotze
M T
MT
Rosenfelder
D
D
Brumfield
A
A
Howells
R
R
Schwartz
R
R
Sylvestri
S
S
Sammon
J
J
Bron
K
K
Orens
P
P
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015179:Colorectal Neoplasms / Q000473:pathology*; D004655:Emulsions; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D004655:Emulsions; D005467:Floxuridine