V600E mutations in metastatic melanoma: Case report.

Abstract

e20002 Background: Vemurafenib, a selective BRAF kinase inhibitor, is a new medicine against carcinoma.This work will discuss new approaches to the treatment of patients with metastatic melanoma, who have been proved to have BRAF V600 mutation. Methods: The 62-year-old patient was initially diagnosed in 2002 when the excision of melanoma of the left calf was performed. HP was Melanoma invasivum nodular, Breslow III, Clark IV, p T3, without angioinvasion. The stadium of illness was M1a (AJCC). Afterwards, she was operated four times. Chemyotherapy was performed with DTIC and in the further treatment secundary HT VLB-BLM-CDDP. In June 2012 the examination of the control ultrasound of the abdomen and pelvis registered the progression of illness. The liver indicated multiple changes of seundary deposit type, the largest of which was 24mm parailiac left lgl 53mm, inguinal left 23mm. It was confirmed that the patient had the mutation on the BRAF gene and she was included in the clinical study in the illness stadium M1c (AJCC). Subsequently the therapy with vemurafenib 960 mg twice a day was introduced, after which side effects were registered: rash gr. 2, arthralgia gr. 1 (pain in the hand joints) and the swelling of ankle joints gr. 1. The patient continued the vemurafenib therapy. At the latest examination in October 2012, the control CT screening registered the regression of secundary deposit by 40%. Results: Identifying the significance of BRAF has led to the development of numerous new medicines against carcinoma. One of them is vemurafenib (PLKS4032), a medicine inhibiting particularly BRAF V600 mutation. Stage I of studying this medicine showed a complete or partial tumor regression in 81% patients with V600 BRAF mutation, while stage showed a relative reduction of death risk in 63% patients, as well as a relative reduction of tumor progression risk in 74% patients in comparison to dakarbazin. Still, patients who take vemurafenib develop resistance to this medicine within 7 months on average. Conclusions: The development of vemurafenib and the role of BRAF targeted therapy in the treatment of metastatic melanoma ensure a new basis for the clinical research. Further clinical studies will research complex molecular mechanisms underlying resistance and toxicity to vemurafenib.