Clinical efficacy and toxicity of standard dose adriamycin in hyperbilirubinaemic patients with hepatocellular carcinoma: relation to liver tests and pharmacokinetic parameters.
A standard dose of Adriamycin (60 mg m-2) was administered to 30 patients with inoperable hepatocellular carcinoma, 16 of whom were hyperbilirubinaemic (18-37 mumol l-1). The hyperbilirubinaemic patients experienced marked myelosuppression, but only minor symptomatic side-effects. The degree of neutropenia was directly related to the serum bilirubin concentration, but not to any other standard liver test, presence or absence of cirrhosis, or any pharmacokinetic parameter studied including the area under the Adriamycin or adriamycinol concentration-time curve to 48 h or infinity, or the terminal half-life of Adriamycin. The area under the log concentration-time curve was significantly greater for both Adriamycin and adriamycinol in patients who were hyperbilirubinaemic compared to those with normal bilirubin. Whilst hyperbilirubinaemic patients may tolerate a full dose of Adriamycin, we found no evidence that this was associated with a better response rate, which was disappointingly low at only 18%.
Johnson
P J
PJ
Institute of Liver Studies, King's College Hospital School of Medicine and Dentistry, London, UK.
Dobbs
N
N
Kalayci
C
C
Aldous
M C
MC
Harper
P
P
Metivier
E M
EM
Williams
R
R
D000328:Adult; D000368:Aged; D001663:Bilirubin / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006932:Hyperbilirubinemia / Q000150:complications / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008113:Liver Neoplasms / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged
D004317:Doxorubicin; D001663:Bilirubin