Clinical pharmacokinetics of epirubicin: the importance of liver biochemistry tests

Twelves, C.; Dobbs, N; Michael, Y; Summers, L. A.; Gregory, Walter M.; Harper, P.; Rubens, R. D.; Richards, MA

doi:10.1038/bjc.1992.353

Cited by 56 publications

(12 citation statements)

References 18 publications

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“…8) In addition, there were some reports that epirubicin clearance correlates with serum aspartate aminotransferase (AST). 9,10) However, these reports show the pharmacokinetics of epirubicin after i.v. injection, and there are few reports after i.a.…”

mentioning

confidence: 88%

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Effect of Acute Hepatic Failure on Epirubicin Pharmacokinetics after Intrahepatic Arterial Injection in Rats

Nagata

Matsuo

Hidaka

et al. 2008

Biological & Pharmaceutical Bulletin

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confidence: 88%

“…9,10) We investigated the effect of acute hepatic failure on the pharmacokinetics of epirubicin in rats. In this study, we showed that acute hepatic failure increased the serum concentration of epirubicin after both i.v.…”

Section: Discussionmentioning

confidence: 99%

Effect of Acute Hepatic Failure on Epirubicin Pharmacokinetics after Intrahepatic Arterial Injection in Rats

Nagata

Matsuo

Hidaka

et al. 2008

Biological & Pharmaceutical Bulletin

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“…The current modifications based principally on serum bilirubin may not be optimal (Twelves et al, 1992). Alternative treatment strategies for patients with abnormal liver tests based on weekly treatment (Twelves et al, 1991) and serum AST (Dobbs et al, 1995) have been proposed.…”

Section: Discussionmentioning

confidence: 99%

Anthracycline doses in patients with liver dysfunction: do UK oncologists follow current recommendations?

Dobbs

Twelves²

1998

Br J Cancer

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Summary The question of whether UK oncologists follow current anthracycline dose modifications when treating patients with liver dysfunction was addressed through a questionnaire. Oncologists were asked the dose of doxorubicin or epirubicin they would prescribe for a woman with breast cancer and liver metastases who had one of four different patterns of abnormal liver chemistry. In each case, the median dose of anthracycline that would have been prescribed was close to that currently recommended. There was, however, wide variation in the dose that oncologists said they would prescribe, some avoiding an anthracycline altogether, whereas others would give full-dose treatment. Medical oncologists would prescribe a significantly lower dose of anthracycline than clinical oncologists for a patient with the most severely disturbed liver tests. Overall, medical oncologists were also significantly more likely to prescribe epirubicin. These results show the need for new, widely accepted anthracycline dose modifications for patients with liver dysfunction.Keywords: liver dysfunction; anthracycline; doxorubicin; epirubicin; dose The anthracyclines, doxorubicin and epirubicin, are among the most widely used cytotoxics in the treatment of adult solid tumours. These drugs are largely eliminated by hepatic metabolism and biliary excretion. Although dose reductions are recommended for patients with liver dysfunction (Pharmacia and Upjohn data sheets), it is not known how widely they have been adopted. Benjamin et al (1973) first reported increased toxicity in eight patients with liver metastases treated with full-dose doxorubicin. This excess toxicity was abrogated in patients with liver dysfunction treated with a reduced dose of doxorubicin. Subsequently, Camaggi et al (1982) showed reduced epirubicin clearance in six patients with liver metastases. These reports led to the current recommendations for doxorubicin and epirubicin doses based on serum bilirubin or bromosulphthalein (BSP) clearance. However, the question of whether liver dysfunction significantly affected anthracycline clearance remained unclear (de Valeriola, 1994) (1996), were invited to reply to a postal questionnaire describing the following clinical situation:'A woman of 50 with early breast cancer was initially treated by conservation surgery with radiotherapy and adjuvant CMF. Three years later she had a cutaneous relapse and was started on tamoxifen. Six months later she developed abdominal pain and was found to have liver metastases on ultrasound scan. Currently she remains quite active and has no evidence of bone metastases but her appetite is reduced. ' The oncologists were told that the aim of the survey was to establish the patterns of anthracycline use in patients with liver metastases and abnormal liver tests. They were also informed that it would be used to establish whether there is a need for new dose recommendations in these patients. The oncologists were asked the dose (as a percentage of full dose) and choice of anthracycline (doxorubicin,...

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“…Based on an evaluation of epirubicin PKs in 53 advanced breast cancer patients, AST is a more sensitive and reliable marker of epirubicin clearance than bilirubin [13]. Using a transaminase-based approach, Dobbs et al [14] identified a target AUC for epirubicin in breast cancer patients with normal liver function, and then validated an AST-based dosing scheme in 16 patients with abnormal liver biochemistry.…”

Section: Epirubicinmentioning

confidence: 99%

Commentary: Oncologic Drugs in Patients with Organ Dysfunction: A Summary

2007

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After completing this course, the reader will be able to:1. Describe the currently recommended dose adjustments for common chemotherapeutics in oncology patients with organ dysfunction.2. Explain the rationale for using phase I dose-escalation studies to determine appropriate chemotherapy dosing in patients with organ dysfunction.3. Discuss the limitations of the currently available studies to guide chemotherapy dose adjustment in patients with organ dysfunction.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTThere are few prospective data regarding the pharmacokinetics and clinical toxicity of commonly used chemotherapeutics in cancer patients with organ dysfunction. Although increasing numbers of studies are investigating newer chemotherapeutics in patients with liver or kidney dysfunction, most guidelines for dosing, especially for established agents, remain empiric. This review describes the available data (both prospective and case study) evaluating the impact of renal and hepatic dysfunction on toxicity and dosing of commonly used chemotherapeutics and provides a practical summary for their use in this setting.

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Clinical pharmacokinetics of epirubicin: the importance of liver biochemistry tests

Cited by 56 publications

References 18 publications

Effect of Acute Hepatic Failure on Epirubicin Pharmacokinetics after Intrahepatic Arterial Injection in Rats

Effect of Acute Hepatic Failure on Epirubicin Pharmacokinetics after Intrahepatic Arterial Injection in Rats

Anthracycline doses in patients with liver dysfunction: do UK oncologists follow current recommendations?

Commentary: Oncologic Drugs in Patients with Organ Dysfunction: A Summary

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