Safety and efficacy of vemurafenib in end stage renal failure

Abstract

BackgroundSerine-threonine inhibitors, such as vemurafenib, are being used increasingly in cancer treatment, and the toxicity and therapeutic benefit need to be balanced carefully both before and during treatment.Case presentationA patient with metastatic melanoma and end stage renal failure who was on peritoneal dialysis was treated with the serine-threonine kinase inhibitor, vemurafenib. After 5 months of treatment, a substantial response to vemurafenib was observed using imaging, but when he developed a prolonged QTc interval (common toxicity criteria (CTC) grade 3), treatment was interrupted. Vemurafenib was restarted at a reduced dose when the QTc interval returned to normal. The patient has had a significant response to vemurafenib and continued on treatment for 12 months after beginning the therapy.ConclusionThis is the first reported case of end stage renal failure in a patient who is taking vemurafenib. Although the patient developed QTc prolongation, it appears to be asymptomatic, and was managed with dose reduction. This case highlights the need for closer QTc monitoring at the start and during treatment.

Long Term Survival and Continued Complete Response of Vemurafenib in a Metastatic Melanoma Patient with BRAF V600K Mutation

“…Previously, this case was reported regarding safety of Vemurafenib in end stage renal failure [ 8 ] and the same case was followed-up for 36 months and showed a sustained complete response even after stopping the BRAF inhibitor treatment. Pivotal BRIM3 trial results indicated sensitivity of Vemurafenib in BRAF V600K mutation [ 2 ].…”

“…Here, we present an extended follow-up of a case of metastatic melanoma which was reported previously that was treated safely in end stage renal failure with Vemurafenib [ 8 ] and now we are reporting the same case after attaining complete remission.…”

“…Tumour infiltrating lymphocytes (TILs) are believed to correlate with outcome, though there is debate about the applicability of this finding for all melanomas [ 12 ]. There is also limited data from randomised trials on the use of Vemurafenib in patients with severe renal impairment, although it is theoretically safe because liver is the major site of metabolism and the safety of Vemurafenib in treating melanoma patient with end stage renal failure was reported previously [ 8 ].…”

“…It has been demonstrated that Vemurafenib pharmacokinetics are not significantly altered by mild to moderate renal dysfunction. There have been no studies on Vemurafenib in patients with severe renal dysfunction except for a case report [ 8 ], as these patients were excluded from randomised clinical trials.…”

Drug Interactions in Palliative Cancer Care and Oncology

“…GlaxoSmithKline, Research Triangle Park, NC;. Finally, vemurafenib is associated with a concentration-dependent QTc interval prolongation, whereas such an impact has not been shown with dabrafenib (Iddawela et al 2013 ).…”