Disposition of Erlotinib and Its Metabolite OSI420 in a Patient with High Bilirubin Levels
In this case report, we describe the therapeutic drug monitoring (TDM) of erlotinib in a patient with abnormally high bilirubin levels with the aim to gain additional information on potentially necessary dose modifications or cessation of drug medication in patients with heavily impaired liver function.\nThe case of a 62-year-old male patient of 77 kg body weight with an adenocarcinoma of the pancreas and metastases in liver and lung is presented. From July 2009 to January 2010, seven cycles of combination chemotherapy consisting of gemcitabine and oxaliplatin were administered. The best response reached under this treatment was a partial response. Thereafter, treatment was discontinued because of hepatic progression of the disease. From March to April 2010, the patient was treated within the frame of a phase I study with an aurora-kinase B inhibitor. Because of progression in form of an increase of pre-existing, and appearance of new, hepatic and pulmonary metastases, the patient did no longer take part in the study. In April 2010, an icterus developed, necessitating an endoscopic retrograde cholangiopancreatography as well as the insertion of a stent to allow recanalisation and elimination of bile and, simultaneously, bilirubin. Nevertheless, despite the attempt of recanalisation of the bile duct, disease progression led to a further increase in bilirubin accompanied by icterus and pruritus.\nAfter informing the patient in detail about the pros and cons of planning any further therapeutic step at all and after extensive discussion, erlotinib was used in the context of the now highly elevated bilirubin levels, with total bilirubin levels of 14.15 mg/dl (normal range 0.1–1.0 mg/dl) and direct bilirubin levels of 11.32 mg/dl (normal range 0.1–0.25 mg/dl), for which experience is lacking and intake of medication therefore not recommended. Written informed consent was obtained from the patient. The patient explicitly agreed to receive erlotinib 150 mg daily for 16 days and additional accompanying blood drawings in order to allow elucidating the pharmacokinetics in this peculiar situation of impaired liver function. The investigation had been approved by the ethical committee.