Pharmacokinetics of intra-arterial mitomycin C with or without degradable starch microspheres (DSM) in the treatment of non-resectable liver cancer.
The effects of degradable starch microspheres (DSM) on mitomycin C pharmacokinetics and bone marrow toxicity were studied in a phase II multicenter study. Sixty-three patients with non-resectable primary or secondary liver cancer were randomized to receive either i.a. mitomycin C 15 mg/m2 first, followed 5 weeks later by mitomycin C 15 mg/m2 plus DSM 360 mg administered into the hepatic artery (group I) or the same treatments in the opposite sequence (group II). In 36 out of 47 patients who received at least 2 treatments, peripheral venous blood samples were analyzed for mitomycin C pharmacokinetics on a minimum of 2 paired courses. In all patients, the area under the concentration time curve (AUC) was significantly lower when the drug was co-administrated with DSM, but the terminal half-life (t1/2) of mitomycin C was unchanged. In group I the addition of DSM resulted in a significantly lowered AUC, but not in group II. The discrepancy between the 2 groups is probably due to differences in DSM-induced intra-hepatic shunting. The addition of DSM resulted in significantly higher platelet nadir values, but unchanged white blood cell count nadir value. In conclusion, DSM reduce the systemic exposure of mitomycin C and seem to lessen the haematologic toxicity judged from a less pronounced decrease in platelets.
Andersson
M
M
Department of Surgery, University Hospital, Umeå, Sweden.
Aronsen
K F
KF
Balch
C
C
Domellöf
L
L
Eksborg
S
S
Hafström
L O
LO
Howell
S B
SB
Kåresen
R
R
Midander
J
J
Teder
H
H
D000328:Adult; D000368:Aged; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D008102:Liver Circulation; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015337:Multicenter Studies as Topic; D011897:Random Allocation; D013213:Starch
D008937:Mitomycins; D016685:Mitomycin; D013213:Starch