Skin toxicity of targeted therapy: Vemurafenib, first experiences from Montenegro

Abstract

Introduction: Data on melanoma inci- dence and mortality in Montenegro is only partially complete. GLOBOCAN and EUCAN reports estimate melanoma incidence in Montenegro to be between 4.6-7.3 cases/100 000. At least 50% of all metastatic melanoma cell lines carry an activating mutation in the BRAF oncogene. The treatment of advanced melanoma with the selecti- ve BRAF inhibitors, such as vemurafenib demonstra- ted improvement in progression free interval and over- all survival when compared to conventional chemothe- rapy treatment. Up to 95% of patients treated with ve- murafenib experience skin toxicity. Material and methods: Five patients with meta- static melanoma have been treated with vemurafenib at the Clinic for Oncology and Radiotherapy Podgorica, Montenegro, during the period 2013-2014. They were treated with standard dose (960 mg twice a day, per os). Data about the occurrence and management of skin si- de-effects in these patients were retrospectively collec- ted from medical charts. Severity of side-effects was graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. Results: In 2013, 41 new cases of melanoma were registered in Montenegro, 20 (48.7%) male and 21 (51.3%) female. In 2014, 49 new cases of melanoma were registered, 27 (55.1%) male and 22 (44.9%) fe- male. Two out of five (40%) vemurafenib treated pati- ents experienced photosensitivity, three (60%) had rash eruptions, four (80%) developed alopecia, and two (40%) had dry skin problems. Alteration in nevus color and size occurred in one (20%) patient, and two (40%) patients developed new pigmented lesions. Conclusion: Skin side effects associated with ve- murafenib are plentiful, but generally manageable with supportive care measures. In our experience, majority of described side-effects were of grade 1 or 2, and none required dose modifications, or discontinuation of the therapy. Our experience suggests that patients taking BRAF inhibitors should have regular full body skin as- sessments, both prior to the beginning of the therapy and periodically after its onset. Clinicians should be aware of the skin related toxicities, in order to minimi- ze their impact on treatment efficacy and patients' qua- lity of life.