Evaluation of First‐Line Sorafenib Treatment for Metastatic Renal Cell Carcinoma in Kidney Transplant Patients: A Single‐Center Experience With Four Cases

To the Editor: The risk of developing renal cancers is reportedly 3–5% among patients with end-stage renal disease preand post-transplantation, which is 100-fold higher than that among the general population (1). Immunosuppressive therapies, which are administered to prevent graft rejection, increase the risk of developing cancers or accelerate tumor cell growth (2). Currently, the treatment strategy for metastatic renal cell carcinoma (mRCC) consists of molecular-targeted therapy. Sorafenib is one of firstline tyrosine kinase inhibitors, and its efficacy has been demonstrated in a previous clinical trial (3). However, clinical information on the use of sorafenib in patients with renal dysfunction, such as those with end-stage renal disease or those who have undergone kidney transplantation, has been limited, because such patients were excluded from the aforementioned trial. We previously reported the efficacy and safety of sorafenib in 20 patients with mRCC undergoing dialysis therapy (1). Our former study indicated that sorafenib treatment seemed feasible (median time to progression: 6.3months; overall survival: 14.2months), although careful monitoring of severe adverse events (AEs) was required (4 of 20 patients [20.0%] discontinued treatment because of ≥grade 3 AEs). Thus, we believe that sorafenib treatment is effective for patients with renal dysfunction. Herein, we describe our single-center experience with first-line sorafenib treatment in four kidney transplant patients with mRCC. Patient characteristics and outcomes are shown in Table 1. All cancers originated from native kidneys. Three patients were pathologically diagnosed as having clear-cell carcinoma. All patients received the same immunosuppressive regimen, including tacrolimus, mycophenolate mofetil, and methylprednisolone at the time of diagnosis. Conversion to a different regimen (i.e., mycophenolate mofetil to everolimus) was performed in three patients. All patients experienced disease progression and died of the cancers. The median times to disease progression and to death were 8.98 and 15.1 months, respectively. AEs were observed in three patients; ≥grade 3 AEs were observed in one patient (25%). During treatment, graft function was stable, and no patient required a major adjustment in the dose of tacrolimus. Previous studies have indicated that the median progression-free survival ranges from 5 to 9 months (3,4), and the median overall survival is 12.5 months in the general population (4). Thus, an equivalent effect of prolonging survival in kidney transplant patients was shown in this study. However, physicians need to pay attention to frequent AEs in these patients compared to the general population (3,4). Moreover, sorafenib treatment had a similar efficacy and toxicity in kidney transplant patients compared to patients with hemodialysis (1). Finally, the present study’s findings may suggest that sorafenib does not affect immunosuppression, because we did not need to modify the dose of tacrolimus. This may be because sorafenib, which is a multi-targeted tyrosine kinase inhibitor of Raf, the vascular endothelial growth factor receptor, and platelet-derived growth factor receptor, is not associated with the mechanism of immunosuppression caused by tacrolimus. However, there may be a possible pharmacokinetic correlation between the two different agents, thus further investigations are needed. In summary, first-line sorafenib treatment seems feasible in kidney transplant patients with mRCC; nevertheless, careful monitoring for AEs is required.