Pharmacokinetics of panitumumab in a patient with liver dysfunction: a case report

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• 作者：L. L. Krens (1)
  J. M. Baas (2)
  F. A. de Jong (3) (4)
  H. J. Guchelaar (1)
  H. Gelderblom (2)
  
• 关键词：Panitumumab ; Liver dysfunction ; Pharmacokinetics ; Colorectal cancer
• 刊名：Cancer Chemotherapy and Pharmacology
• 出版年：2014
• 出版时间：February 2014
• 年：2014
• 卷：73
• 期：2
• 页码：429-433
• 全文大小：283 KB
• 作者单位：L. L. Krens (1)
  J. M. Baas (2)
  F. A. de Jong (3) (4)
  H. J. Guchelaar (1)
  H. Gelderblom (2)
  
  1. Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, PO Box 9600 NL, 2300 RC, Leiden, The Netherlands
  2. Department of Clinical Oncology, Leiden University Medical Center, PO Box 9600 NL, 2300 RC, Leiden, The Netherlands
  3. Medical Department, Amgen B.V., P.O. Box 3345, 4800 DH, Breda, The Netherlands
  4. HQ Medical Affairs, Merck Serono, Frankfurter Strasse 250, 64293, Darmstadt, Germany
  
• ISSN：1432-0843

文摘

Purpose Panitumumab is used for the treatment for metastatic RAS wild-type colorectal cancer (mCRC). It is likely that many of these patients will present with liver metastases and some with liver dysfunction. The pharmacokinetics in patients with hepatic impairment has not been investigated, and dosage adjustments are undetermined. Here, we present a case of a patient with progressive mCRC and liver dysfunction. Methods A heavily pretreated KRAS wild-type mCRC patient with liver disease Child-Pugh class B was treated with 2-weekly intravenous panitumumab (6?mg/kg). The patient received 2 doses of 490?mg i.v. panitumumab after which progressive disease was documented. Toxicities were graded using CTCAEv4.0. Serum samples were collected, and panitumumab concentrations were determined using a validated immunoassay. Pharmacokinetic parameters after the first dose, including dose-normalized AUC from time zero–day 14, clearance (CL), and elimination half-life (T1/2), were estimated via trapezoidal noncompartmental methods. Data were compared to historical data from a population with adequate liver function, as reported by Stephenson (Clin Colorectal Cancer, 8:29-7, 2009). Values within the range of the mean ±1 standard deviation (SD) were considered not deviant. Results Calculated AUC after the first dose of 6?mg/kg panitumumab in this patient with hepatic dysfunction was 877?μg?day/mL (Stephenson’s cohort 1: 744?±?195?μg?day/mL). Estimated T1/2 was 3.58?days (5.28?±?1.90?days), and CL was 6.9?mL/day/kg (8.21?±?3.79?mL/day/kg). Estimated PK parameters during the first cycle were inside reported mean ±1 SD of historical controls without liver dysfunction. No toxicity was reported during treatment; particularly, no diarrhea and skin toxicity were noticed. Conclusions The pharmacokinetics of panitumumab in this patient suffering from metastatic colorectal cancer with liver dysfunction Child-Pugh class B was similar compared to patients with adequate liver function. Moreover, no substantial toxicity was detected. The here-presented data may help clinical decision making in real-life practice. Two-weekly panitumumab monotherapy seems to be safely applicable in patients with KRAS wild-type mCRC and hepatic dysfunction, without the need for any dose adjustments.