Se events were observed other than anorexia (grade 1). Although the dosereduction of 5-FU was not recommended in previous studies [46, 59, 60], these studies indicated that a further accumulation of cases is needed to establish the optimal dose in HD patients. Particular attention should also be paid to the development of 5-FU-induced encephalopathy, especially when a higher dose of 5-FU is administered. Ammonia, a metabolite of 5-FU, accumulates in large amounts after the administration of high-dose 5-Kitai et al. Renal Replacement Therapy (2016) 2:Page 7 ofFU [61, 62]. Renal dysfunction may be an aggravating factor of hyperammonemia related to 5-FU infusion [63, 64]. It has been suggested that a large amount of fluoroacetate, a final metabolite of 5-FU, could be accumulated in patients with renal dysfunction and inhibit the Krebs cycle. This could cause impairment in the ATPdependent urea cycle, resulting in lactic acidosis and further exacerbation of a hyperammonemic state [62, 64]. The direct toxicity of alpha-fluoro-beta-alanine (FBAL), an intermediate metabolite of 5-FU, on myelin was also proposed as the cause of 5-FU-induced encephalopathy [65]. In HD patients, FBAL, which is mainly excreted by the kidney with minor elimination via bile and the bowel, was reported to accumulate approximately twofold higher than expected in patients with normal renal function [66]. The authors also reported that FBAL could be eliminated by HD, suggesting that more intensive dialysis treatment may be useful for improving the elimination of FBAL to minimize the possible risks of FBAL-mediated toxicity.Tyrosine kinase inhibitorsSeveral studies have recently examined the pharmacokinetics of tyrosine kinase inhibitors such as sunitinib, imatinib, sorafenib, and erlotinib in HD patients [67?71]. After oral administration, these agents are primarily metabolized in the liver by cytochrome CYP3A4, with only a small proportion excreted in the urine [72, 73]. These agents were reported to be minimally affected by HD [67, 69?1]. Therefore, administration can take place anytime, independent of the HD sessions. Previous studies have shown that treatment with these agents is well tolerated and has good efficacy in patients with ESRD [71, 72, 74, 75]. However, one study showed that dose reduction or discontinuation of sorafenib was frequently needed (even with lower concentrations of sorafenib) in patients with metastatic renal cell carcinoma undergoing Nelfinavir (Mesylate) HD [70]. Serious adverse events were found in 9 of 10 patients, including a grade 5 subarachnoid hemorrhage and a grade 4 cerebellar hemorrhage. The authors suggested that the patients on chronic HD might be susceptible to the unfavorable effects of antiangiogenic agents like sorafenib due to their vulnerable vascular tissues. Treatment of HD patients with tyrosine kinase inhibitors appears to be feasible, but special attention should be paid to the occurrence of serious adverse events, considering the underlying risk factors of HD patients.provided recent evidence for cancer risk and screening in the ESRD population. There is a pressing need for clinical trials that are designed to identify those who would benefit from cancer screening PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/17139194 in this population. This review article also addressed the pharmacokinetics of representative anti-cancer agents, carboplatin, 5-FU, and tyrosine kinase inhibitors. Although the optimal interval between dialysis sessions and carboplatin infusion has not been fully investigated, th.