Hepatotoxicity of temsirolimus and interferon alpha in patients with metastasised renal cancer: A case study

Abstract

Temsirolimus is a drug used for the treatment of renal cell carcinoma. The target of action of temsirolimus is mTOR (mammalian target of rapamycin) kinase, a cellular protein that regulates the growth of tumour cells and blood vessels. The aim of the present study was to determine whetherif temsirolimus has greater hepatotoxic potential than standard therapies for renal cancer, including interpheron alpha and vinblastine. The current study was conducted on patients treated at the Institute for Radiology and Oncology of Serbia, Belgrade for metastasised renal cell carcinoma. In total, nine patients were administered 25 mg of temsirolimus per week for four weeks. Another fourteen patients were treated with standard therapy, including interferon alpha (6 MJ, three times a week) and vinblastine (10 mg two days per cycle, for four cycles). Biochemical parameters of liver function (aspartate amino-transferase, alanine amino-transferase, alkaline phosphatase, lactate dehydrogenase, γ glutamine trans-peptidase, bilirubine [direct and total] and serum proteins) were analysed prior to administration and four weeks after treatment. In total, six patients developed hepatotoxicity, which was defi ned as a 3-fold increase in aspartate amino-transferase and alanine amino-transferase levels after the administration of therapy. Three patients showing signs of hepatotoxicity received temsirolimus, and three were treated with interferon alpha and vinblastine. Except for the level of aspartate amino-transferase, the studied factors including age, sex, drug diabetes, heart failure, hypertension, nephrectomy, stage of cancer and serum urea and creatinine levels were not associated with hepatotoxicity. Namely, in patients who experienced hepatotoxicity, the aspartate amino-transferase content was signifi cantly lower prior to the administration of drugs (13.3±6.1 vs. 20.1±7.4; T = -2.400, df = 12, p = 0.033). The results of the present case study suggest that temsirolimus is not more hepatotoxic in patients with metastasised renal cancer than standard therapies such as interferon alpha and vinblastine.