Pharmacokinetics of 5-fluorouracil in colorectal cancer patients receiving interferon.
BACKGROUND
The outlook for patients with advanced colorectal cancer remains poor. Recent reports of the combination of 5-fluorouracil (5-FU) and alpha-interferon in colorectal cancer have suggested better response rates. One possible explanation for interaction between 5-FU and interferon is that interferon alters the pharmacokinetics of 5-FU, increasing plasma 5-FU levels.


METHODS
To investigate the possibility of interaction between the two agents, steady state 5-FU pharmacokinetics was evaluated in patients with colorectal cancer who received 5-FU by continuous i.v. infusion with and without concurrent administration of subcutaneous alpha-interferon. 5-FU levels were measured by reverse-phase high-performance liquid chromatography.


RESULTS
Twenty-six patients were evaluated. There were 4 partial responses (15%). There was no significant difference in steady state 5-FU levels whether or not alpha-interferon was administered concurrently.


CONCLUSIONS
Any synergistic activity that may exist between this combination of 5-FU and alpha-interferon is not simply due to altered 5-FU pharmacokinetics.
Pittman
K
K
Department of Clinical Medicine, St. James's University Hospital, Leeds, U.K.
Perren
T
T
Ward
U
U
Primrose
J
J
Slevin
M
M
Patel
N
N
Selby
P
P
D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000097:blood / Q000378:metabolism* / Q000628:therapy; D003131:Combined Modality Therapy; D004357:Drug Synergism; D005472:Fluorouracil / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008875:Middle Aged; D011994:Recombinant Proteins
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D005472:Fluorouracil