is not recommended as a standard adjuvant treatment for melanoma. A 2013 meta-analysis suggested that the addition of interferon alpha increased disease-free and overall survival for people with AJCC TNM stage II-III cutaneous melanoma. A 2011 meta-analysis showed that interferon could lengthen the time before a melanoma comes back but increased survival by only 3% at 5 years. The unpleasant side effects also greatly decrease quality of life. In the European Union, interferon is usually not used outside the scope of clinical trials. Chemotherapy Chemotherapy drugs such as Dacarbazine have been the backbone of metastatic melanoma treatment since FDA approval in 1975; however, its efficacy in terms of survival has never been proven in an RCT. In people with locally advanced cutaneous malignancies and sarcoma, isolated limb infusion (ILI) has been found to be a minimally invasive and well-tolerated procedure for delivering regional chemotherapy. Targeted therapy Melanoma cells have mutations that allow them to survive and grow indefinitely in the body. Small-molecule targeted therapies work by blocking the genes involved in pathways for tumor proliferation and survival. The main treatments are BRAF, C-Kit and NRAS inhibitors. These inhibitors work to inhibit the downstream pathways involved in cell proliferation and tumour development due to specific gene mutations. People can be treated with small-molecule targeted inhibitors if they are positive for the specific mutation. BRAF inhibitors, such as vemurafenib and dabrafenib and a MEK inhibitor trametinib are the most effective, approved treatments for BRAF positive melanoma. Melanoma tumors can develop resistance during therapy which can make therapy no longer effective, but combining the use of BRAF and MEK inhibitors may create a fast and lasting melanoma therapy response. A number of treatments improve survival over traditional chemotherapy. Biochemotherapy (chemotherapy with cytokines IL-2 and IFN-α) combined with BRAF inhibitors improved survival for people with BRAF positive melanoma. Biochemotherapy alone did not improve overall survival and had higher toxicity than chemotherapy. Combining multiple chemotherapy agents (polychemotherapy) did not improve survival over monochemotherapy. Targeted therapies result in relatively short progression-free survival (PFS) times. The therapy combination of dabrafenib and trametinib has a 3-year PFS of 23%, and 5-year PFS of 13%. Immunotherapy Immunotherapy is aimed at stimulating the person's immune system against the tumor, by enhancing the body's own ability to recognize and kill cancer cells. The current approach to treating melanoma with immunotherapy includes three broad categories of treatments including cytokines, immune check point