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ABSTRACT: The pharmacokinetics and clinical activity of epirubicin were investigated in 16 patients with hepatocellular carcinoma (HCC) who received epirubicin at 75 mg/m2; the drug was given intravenously to 7 patients and via the hepatic artery to 9 patients (7 of whom also underwent embolisation). Lignocaine (1 mg/kg) was also given intravenously to 15 patients, and the metabolite monoethylglycinexylidide (MEGX) was measured as an indicator of liver function. Epirubicin clearance correlated with serum aspartate aminotransferase (AST), albumin and bilirubin values in patients treated intravenously or intraarterially. Although the route of administration did not affect the median total plasma clearance of epirubicin, early- and intermediate-phase clearance was higher following intraarterial administration. MEGX levels correlated with serum bilirubin levels but there was no correlation with albumin or AST values or epirubicin clearance. The rate of response to epirubicin was 3/13 (23%; 95% confidence interval, 8%-50%). Intravenous epirubicin was tolerated well, but intraarterial treatment was associated with significant morbidity. These data confirm that although current recommended dose adjustments are based primarily on serum bilirubin levels, altered epirubicin pharmacokinetics correlate more strongly with AST and albumin values than with serum bilirubin concentrations. However, at this dose and schedule, epirubicin has only modest activity against HCC.
Cancer Chemotherapy and Pharmacology 02/1994; 34(5):405-10. · 2.83 Impact Factor
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ABSTRACT: 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%.
British Journal of Cancer 06/1992; 65(5):751-5. · 5.04 Impact Factor
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ABSTRACT: To determine the effect of coadministration of lipiodol on the pharmacokinetics and systemic toxicity of intraarterial Adriamycin in patients with hepatocellular carcinoma, nine patients were studied in detail. Each received two courses of a bolus injection of Adriamycin (60 mg/m2), in one of which the Adriamycin was mixed with 10 ml of lipiodol. Analysis of the paired data, and additional 'non-paired' data from a further seven patients, showed that there was no significant difference in the area under the concentration-time curve for Adriamycin or adriamycinol or, in the case of Adriamycin, the terminal half-life. Likewise the fall in haemoglobin concentration, white cell count and platelet count following treatment, and the degree of nausea and vomiting were not significantly different. Comparison with a series of 12 patients receiving intravenous Adriamycin, in the same dose schedule, revealed no difference in terms of pharmacokinetic parameters or toxicity with intraarterial administration of Adriamycin, with or without lipiodol.
Journal of Hepatology 08/1991; 13(1):120-7. · 9.26 Impact Factor
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ABSTRACT: The technique of 'targeting' cytotoxic drugs by mixing them with the contrast medium lipiodol is now widely used in Japan and the Far East where it has been reported to enhance response rates in patients with hepatocellular carcinoma. In the present study 19 patients with this tumour were treated with intra-(hepatic) arterial adriamycin (60 mg/m2), at least one course of which was combined with lipiodol (10-20 ml). Two patients (11%) had a remission as indicated by a significant fall in serum alphafetoprotein and there was a reduction of tumour size in one of these. The median survival period was 3 months (range 1-18) with the two responding patients surviving 8 and 12 months. This response rate was no better than the figure of 14% seen in 31 consecutive patients treated with intravenous adriamycin at the same dose, and the survival curves of the two groups of patients were not significantly different. Lipiodol in combination with adriamycin is not superior to intravenous adriamycin administered alone.
Journal of Hepatology 12/1990; 11(3):349-53. · 9.26 Impact Factor
