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Pharmacokinetics of dabrafenib in a patient with metastatic melanoma undergoing haemodialysis
Author(s) -
Park John J.,
Boddy Alan V.,
Liu Xiaoman,
Harris David,
Lee Vincent,
Kefford Richard F.,
Carlino Matteo S.
Publication year - 2017
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12557
Subject(s) - dabrafenib , trametinib , medicine , pharmacokinetics , melanoma , oncology , metastatic melanoma , cancer research , vemurafenib , mapk/erk pathway , biology , kinase , microbiology and biotechnology
Summary 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 .