Bortezomib in patients with renal impairment

Renal failure is a common manifestation of multiple myeloma (MM). Bortezomib is primarily metabolized by cytochrome p450 isoforms. It also has a cytochrome-independent metabolism by excretion through the bile and kidney. Based on our observations, we aimed to explore the efficacy and toxicity profiles of bortezomib in 56 patients with MM, 24 of which had moderate to severe renal failure. Overall response and complete response, as well as very good partial response rates, were comparable between patients with normal renal functions and renal impairment. The median overall survivals for patients with estimated glomerular filtration rates of <60 and ≥60 ml/minute were similar. Although there was a tendency for shorter overall survival along lower estimated glomerular filtration rates, this difference did not reach a statistical significance. Overall and severe adverse events, and dose modification and treatment discontinuation rates were higher in patients with renal impairment. Patients with renal failure had more thrombocytopenia and diarrhea. While thrombocytopenia was mild to moderate and manageable, diarrhea, which led to serious adverse events, was more severe in patients with renal failure who received bortezomib as monotherapy. Bortezomib appears to be active; however, when used alone, it may cause more frequent and severe adverse events in patients with MM and renal failure.     

Fas-1377A/G and FasL-844 T/C gene polymorphisms and epithelial ovarian cancer

BACKGROUND: The Fas receptor is known to be widely expressed in various tissues and FasL is highly expressed on cells of the immune system and also on cells of immune-privileged areas such as the eyes and brain. Ovarian cells are known to exhibit marked FasL immunoreactivity throughout follicular development; there may also be a relationship between Fas and FasL polymorphisms and the immune privileges of the epithelial ovarian cells. PATIENTS AND METHODS: The study included 47 epithelial ovarian carcinoma patients and 41 healthy subjects. Polymerase chain reaction (PCR) and restriction endonucleases were used to determine the polymorphic Fas and FasL genes. RESULTS: The FasL CC genotype was found to increase the risk of ovarian carcinoma and a protective effect of the GGCT genotype was observed. CONCLUSION: Because of the expressional aspects of the FasL-844T --> C polymorphism, individuals carrying the FasL-844C allele would be expected to have higher FasL expression on tumour cells compared with those carrying the FasL-844T allele. People with such a genotype show a tendency to develop various tumours.