An Alternative Therapy for Patients with Hepatic Impairment?

Patients with advanced cancer in the setting of liver dysfunction pose a real challenge for physicians, as many cancer chemotherapeutic agents undergo hepatic metabolism and their administration to patients with hepatic impairment often leads to compromise of patient safety. A large proportion of patients with colorectal cancer either present with or develop liver metastases and as a result, many of them have suboptimal liver function [1]. In this issue of O NKOLOGIE Moosmann et al. [2] present a case of a patient with diffuse liver metastases secondary to carcinoma of the colon who was treated successfully with the combination of bevacizumab and cetuximab despite having abnormal liver function parameters. This patient had previously failed capecitabine and oxaliplatin combination chemotherapy, making irinotecan-based chemotherapy with or without a targeted agent the standard second-line choice. However, this patient’s bilirubin level was markedly elevated at 12.8 mg/dl, aspartate transaminase was elevated 8 times the upper limit of normal (ULN) at 390 U/l and the alanine transaminase was mildly elevated. Irinotecan’s main metabolite, SN-38, is cleared primarily via liver glucuronidation and in the biliary system and several studies have shown that patients with bilirubin levels greater than 1.5 times ULN and transaminases greater than 5 times ULN were most susceptible to irinotecan toxicities. [3, 4]. Thus, irinotecan was not a viable option for this patient and most oncologists, faced with a similar situation, would probably have offered supportive care. In this case, the authors opted to treat this patient with cetuximab and bevacizumab combined and achieved reduction in liver metastases. This was associated with a decrease of the bilirubin level to 1.9 mg/dl after 8 weeks of therapy, eventually rendering the patient amenable to further treatment with irinotecan-based chemotherapy. Despite limited data on their use in colon cancer, the combined use of an epidermal growth factor (EGFR) inhibitor,