Efficacy and safety of sorafenib for treatment of Japanese metastatic renal cell carcinoma patients undergoing hemodialysis.

BACKGROUND: Little information has been published on the use of tyrosine kinase inhibitors for treatment of patients undergoing hemodialysis (HD). We investigated the efficacy and safety of sorafenib for metastatic renal cell carcinoma (mRCC) patients undergoing HD. METHODS: Twenty patients undergoing HD were treated with sorafenib as first-line therapy for mRCC at our hospital between April 2008 and August 2014. Patient medical records were retrospectively reviewed to evaluate the response to sorafenib and treatment-related toxicity. RESULTS: Fifteen and 5 patients were classified in the intermediate and poor risk groups, respectively, of the Memorial Sloan-Kettering Cancer Center risk model. Eighteen patients had 3 or more metastatic lesions, and 7 patients had metastases in 2 or more organs. Of 16 patients who had previously undergone nephrectomy, 8 were pathologically diagnosed with non-clear-cell carcinoma. The median duration of sorafenib therapy was 4.7 months. Sorafenib was discontinued owing to progressing disease for 15 patients and because of serious adverse events (AE) (≥grade 3) for 4 patients, i.e. subarachnoid hemorrhage, cerebral hemorrhage, sepsis, and syncope for 1 patient each. Median time to progression was 6.3 months, and median overall survival was 14.2 months. CONCLUSIONS: In this study, many patients had unfavorable clinical features, for example poor risk classification and metastases in multiple organs. Although sorafenib treatment of HD patients seems feasible, careful monitoring is needed because of the tendency for a high incidence of serious AE, even when a reduced dose is administered.

Comparison of survival rates in patients with metastatic renal cell carcinoma according to treatment era including cytokine and targeted therapy.

We compared the survival rates in patients with metastatic renal cell carcinoma between the cytokine and molecular targeted therapy era. The study included 321 patients who were diagnosed with metastatic renal cell carcinoma between 1987 and 2011. The patients were divided into two groups according to when they started therapy for metastatic renal cell carcinoma: in the cytokine era (1987-2007) and in the targeted therapy era (after 2008). The beginning of the follow-up period was defined as the time of discovery of metastasis occurrence. Cytokine and targeted therapy eras included 235 and 86 patients, respectively. Seventy-five percent of the patients in the cytokine era actually received cytokine therapy. Eighty-one percent of the patients in the targeted therapy era received targeted therapy and 14% received both cytokine and targeted therapy. There were no significant differences in overall survival rates (cytokine 29 months, targeted 38 months, P = 0.1789).

Brain metastasis in a patient with a sarcomatoid variant RCC with well-controlled extracerebral metastases by temsirolimus.

BACKGROUND: The sarcomatoid variant of metastatic renal cell carcinoma (RCC) has often an aggressive course and a poor prognosis, particularly when accompanied with brain metastasis. CASE REPORT: We describe the case of a patient with sarcomatoid variant RCC in whom brain metastasis was observed as a new lesion during treatment with temsirolimus, despite other extracerebral metastatic lesions being well-controlled and progression-free. RESULTS: This discrepancy between the effectiveness of temsirolimus for extracerebral metastases and the simultaneous progression of brain metastases of RCC raises a concern that while vascular endothelial growth factor (VEGF)-targeted therapy may have clinical efficacy, it may also carry a risk for new brain metastases due to weakening of the structure of the blood brain barrier. CONCLUSION: This case indicates that computed tomography monitoring of the brain should be regularly performed during VEGF-targeted therapy in patients with sarcomatoid variant RCC, even if brain metastases are absent and extracerebral metastatic lesions are well controlled.

Clinical results and pharmacokinetics of sorafenib in chronic hemodialysis patients with metastatic renal cell carcinoma in a single center.

OBJECTIVE: We investigated the safety and feasibility of sorafenib in patients with end-stage renal disease undergoing hemodialysis by examining the influence of pharmacokinetic parameters to their benefit and also the occurrence of drug-related adverse events of sorafenib. METHODS: Ten patients with metastatic renal cell carcinoma undergoing hemodialysis received sorafenib. Initial dose was 200 mg once daily, and the dose was increased up to the maintenance dose of 200 mg twice daily. The pharmacokinetic study was performed after a steady state was reached with 200 mg twice daily in six patients. RESULTS: Complete response occurred in one patient, partial response in three, stable disease in four and progressive disease in two. Median progression-free survival was 6.3 months. Serious adverse events were found in nine patients, including a Grade 5 subarachnoid hemorrhage and a Grade 4 cerebellar hemorrhage. In the pharmacokinetic study, the geometric mean of maximum concentration and area under the curve from 0 to 10 h of plasma concentration were similar on the day of hemodialysis and the day off hemodialysis. These data were lower than those from Japanese people with healthy kidneys and normal kidney function. There was no association between objective response or the occurrence of serious adverse events and pharmacokinetic parameters. CONCLUSIONS: Treatment with sorafenib of patients with metastatic renal cell carcinoma undergoing hemodialysis appears to be feasible, but we express some concern about the higher incidence of serious adverse events even with the reduced dose. However, clinical efficacy was not compromised.

Proteinuria-reducing effects of tonsillectomy alone in IgA nephropathy recurring after kidney transplantation.

BACKGROUND: Few studies have been conducted to determine the efficacy of tonsillectomy in suppressing IgA nephropathy recurring after the kidney transplantation. MATERIALS AND METHODS: Of the 405 kidney recipients who received allograft transplants at our institution between 1998 and 2005, 63 (63 of 405, 16%) were diagnosed as having recurrence of IgA nephropathy in the kidney graft. Among the 63 patients, our subjects in this study were 28 patients who were confirmed to have recurrence of IgA nephropathy by histopathological examination, and who had persistent urinary protein excretion levels of more than 300 mg/day despite medical treatments. Sixteen patients (group 1) underwent tonsillectomy alone, whereas the remaining 12 patients (group 2) did not receive tonsillectomy. The degree of proteinuria, kidney graft function, and blood pressure were analyzed retrospectively in the two patient groups. RESULTS: The urinary protein excretion decreased dramatically after the tonsillectomy in all of the 16 patients of group 1 (880+/-630 mg/day to 280+/-220 mg/day, P<0.01) but none of group 2. The reduction in urinary protein excretion after tonsillectomy was especially marked in the patients with mild mesangial changes, such as minor glomerular abnormalities, when compared with that in patients with severe mesangial changes, such as diffuse proliferative glomerular abnormalities (mean percent decrease in the urinary protein excretion rate at 12 months after tonsillectomy; 31% minor glomerular abnormalities vs. 62% diffuse proliferative glomerular abnormalities, P<0.01). CONCLUSION: These results suggest that in patients receiving oral immunosuppressive therapy for recurrence of IgA nephropathy after the kidney transplantation, reduction of the urinary protein excretion can be expected with tonsillectomy alone, without accompanying pulsed steroid therapy.

Kidney transplantation in a recipient with anti-HLA antibody IgM positive.

In general, anti-HLA antibody belongs to the IgG subclass, but there are very few reports of detection of anti-HLA IgM antibodies. In the present study, we report a renal transplant recipient with a positive NIH-complement dependent cytotoxicity (NIH-CDC) test. The patient was a 24-year-old male with focal segmental glomerulosclerosis (FSGS) as the underlying kidney disease. He had been on maintenance hemodialysis since December 2003 and finally received a living-donor allograft from his mother in October 2008. Pre-transplantation, the NIH-CDC test was positive for both B and T cells, but the flow-cytometric crossmatch test (FCXM) was negative for both cells. The result of the panel-reactive antibody assay (PRA)-single beads test using anti-IgM antibody as the second antibody demonstrated that the positive NIH-CDC test was due to the presence of anti-HLA IgM antibody against the donor-specific antigen A24. Biopsy specimens showed thrombus formation in a small number of glomeruli immediately after the transplantation, but this finding was no longer seen at three months postoperatively. We report successful renal transplantation in a case with anti-HLA IgM antibody.