title: Pharmacokinetics of dabrafenib in a patient with metastatic melanoma undergoing haemodialysis.
abstract: The combination of dabrafenib and trametinib is a standard of care for the management of BRAF mutant metastatic melanoma. Clinical trials excluded patients with end-stage kidney disease (ESKD), and as such, no data are available regarding the safety, efficacy and pharmacokinetics of these drugs in such patients. Here, we present the case of a 78-yr-old male patient with ESKD managed with haemodialysis (HD), treated with dabrafenib and trametinib at reduced doses. The patient has had a partial response, and this response continues at 9 months since our last follow-up without any dose escalation. Treatment was complicated by the development of diarrhoea, attributed to trametinib, necessitating temporary cessation of trametinib. Pharmacokinetic profiling of dabrafenib was undertaken, and its metabolites were similar pre- and post-dialysis and comparable to those in patients with normal renal function. Moreover, HD did not lower the plasma concentration of dabrafenib or trametinib. It is feasible to administer dabrafenib, in combination with trametinib, to patients with ESKD undergoing HD.
authors.affiliation: Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW, Australia.
authors.forename: John J
authors.initials: JJ
authors.lastname: Park
authors.affiliation: University of Sydney, Sydney, NSW, Australia.
authors.forename: Alan V
authors.initials: AV
authors.lastname: Boddy
authors.affiliation: University of Sydney, Sydney, NSW, Australia.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Liu
authors.affiliation: University of Sydney, Sydney, NSW, Australia.|Department of Renal Medicine, Westmead Hospital, Westmead, NSW, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Harris
authors.affiliation: University of Sydney, Sydney, NSW, Australia.|Department of Renal Medicine, Westmead Hospital, Westmead, NSW, Australia.
authors.forename: Vincent
authors.initials: V
authors.lastname: Lee
authors.affiliation: Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW, Australia.|Department of Clinical Medicine, Macquarie University, Sydney, NSW, Australia.|Melanoma Institute Australia, Sydney, NSW, Australia.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Kefford
authors.affiliation: Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW, Australia.|University of Sydney, Sydney, NSW, Australia.|Melanoma Institute Australia, Sydney, NSW, Australia.
authors.forename: Matteo S
authors.initials: MS
authors.lastname: Carlino
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008545:Melanoma / Q000150:complications / Q000188:drug therapy / Q000556:secondary*; D010091:Oximes / Q000008:administration & dosage; D011728:Pyridones / Q000008:administration & dosage; D011744:Pyrimidinones / Q000008:administration & dosage; D006435:Renal Dialysis; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D010091:Oximes; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib; C561627:dabrafenib
keywords: dabrafenib; haemodialysis; melanoma; pharmacokinetics; trametinib