Pharmacokinetics of recombinant human interferon-alpha 2a combined with 5-fluorouracil in patients with advanced colorectal carcinoma.
We evaluated the pharmacokinetics of 5-fluorouracil (5-FU) combined with recombinant human interferon (IFN)-alpha 2a in 10 previously untreated patients with advanced colorectal carcinoma. 5-FU was administered as a continuous i.v. infusion, 750 mg/m2/day for 5 days during week 1. One s.c. injection of IFN-alpha 2a, 9 x 10(6) IU, was administered during week 2. Beginning with week 3, a continuous i.v. infusion of 5-FU 750 mg/m2/day for 5 days was administered in combination with IFN-alpha 2a, 9 x 10(6) IU s.c. three times per week. The combination of 5-FU and IFN-alpha 2a was continued every other week until either 3 months after complete remission or tumor progression. No grade 4 toxicity was observed. Granulocytopenia (two patients), leukopenia (one patient), thrombocytopenia (one patient), stomatitis (two patients), fatigue (one patient) and hand-foot syndrome (one patient) were the major (grade 3) toxic reactions encountered. Overall, one complete and six partial responses were noted. The results of the paired t-test showed no statistically significant differences between the means of the two treatments, 5-FU and 5-FU plus IFN-alpha 2a, with respect to the steady-state plasma concentration, area under the concentration-time curve, total body clearance, or steady-state volume of distribution of 5-FU, or the serum concentration of IFN. We conclude that 5-FU and IFN-alpha 2a do not interact pharmacokinetically at the doses and schedules in the regimen studied.
Kim
J
J
Division of Medicine, University of Texas MD Anderson Cancer Center, Houston 77030, USA.
Zhi
J
J
Satoh
H
H
Koss-Twardy
S G
SG
Passe
S M
SM
Patel
I H
IH
Pazdur
R
R
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D007262:Infusions, Intravenous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D016896:Treatment Outcome
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D005472:Fluorouracil