Treatment: Malignant Melanoma

Early recognition and local excision for localized disease is best; 1- to 2-cm margins are as effective as 4- to 5-cm margins and do not usually require skin grafting. Elective lymph node dissection offers no advantage in overall survival compared with deferral of surgery until clinical recurrence. Pts with stage II disease may have improved disease-free survival with adjuvant interferon (IFN)-α 3 million units three times weekly for 12-18 months. In one study, pts with stage III disease had improved survival with adjuvant IFN, 20 million units IV daily × 5 for 4 weeks, then 10 million units SC three times weekly for 11 months. This result was not confirmed in a second study. Metastatic disease may be treated with chemotherapy or immunotherapy. Vemurafenib 960 mg PO bid or dabrafenib 150 mg PO bid induces responses in about 50% of pts with BRAF mutations. Median survival is about 16 months. Addition of a MET inhibitor (trametinib 2 mg/d) improved response rate to 64% and median overall survival to >20 months. The anti-CTLA4 antibody ipilimumab prolongs survival by about 4 months. The combination of ipilimumab and the PD-1 blocker nivolumab induced responses in both BRAF mutant and BRAF wild-type tumors. Response rate 58% with responses lasting about 12 months. Dacarbazine (250 mg/m² IV daily × 5 q3w) plus tamoxifen (20 mg/m² PO daily) may induce partial responses in one-quarter of pts. IFN and interleukin 2 (IL-2) at maximum tolerated doses induce partial responses in 15% of pts. Rare long remissions occur with IL-2. Temozolomide is an oral agent that has some activity. It can enter the central nervous system (CNS) and is being evaluated with radiation therapy for CNS metastases. No therapy for metastatic disease is curative. Vaccines and adoptive cellular therapies are being tested.