Park John J, Boddy Alan V, Liu Xiaoman, Harris David, Lee Vincent, Kefford Richard F, Carlino Matteo S
Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW, Australia.
University of Sydney, Sydney, NSW, Australia.
Pigment Cell Melanoma Res. 2017 Jan;30(1):68-71. doi: 10.1111/pcmr.12557.
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.
达拉非尼与曲美替尼联合用药是治疗BRAF突变转移性黑色素瘤的标准治疗方案。临床试验排除了终末期肾病（ESKD）患者，因此，尚无关于这些药物在这类患者中的安全性、疗效和药代动力学的数据。在此，我们报告一例78岁男性ESKD患者，该患者接受血液透析（HD）治疗，以降低剂量接受达拉非尼和曲美替尼治疗。患者出现部分缓解，自我们上次随访以来，这种缓解持续了9个月，且未进行任何剂量递增。治疗过程中出现腹泻，归因于曲美替尼，需要暂时停用曲美替尼。对达拉非尼进行了药代动力学分析，其代谢产物在透析前后相似，且与肾功能正常患者的代谢产物相当。此外，血液透析并未降低达拉非尼或曲美替尼的血浆浓度。对于接受血液透析的ESKD患者，联合使用达拉非尼和曲美替尼是可行的。
