title: Algorithm for the management of metastatic cutaneous melanoma.
abstract: Over the last 4 years, various drugs have been approved for the treatment of metastatic cutaneous melanoma. Ipilimumab, an anti-CTLA-4 inhibitor that stimulates antitumor immunity, was the first agent to improve overall survival both in first line and in previously treated patients. Ipilimumab results in long term disease control in approximately 20% of the patients. Vemurafenib was the first BRAF inhibitor (BRAFi) approved and also resulted in improved overall survival compared with dacarbazine in patients with BRAF mutated metastatic melanoma. More recently, another BRAFi, dabrafenib, and a MEK inhibitor, trametinib, were approved either alone or in combination as they each showed significant antitumor activity relative to dacarbazine and the combination appeared superior to dabrafenib monotherapy. The major feature of such tumor targeted therapy is its high response rate (40-70%) and the rapidity of the responses, resulting in prompt clinical improvement. However, unlike immunotherapy, targeted therapy does not result in long-term treatment free survival. In this paper, we discuss how best to integrate the currently available treatment options including high-dose interleukin-2 (HD IL-2), systemic chemotherapy, ipilimumab and tumor targeted therapy in various clinical scenarios.
authors.affiliation: Centro Oncológico Antonio Ermírio de Moraes, São Paulo, Brazil. buzaidac@yahoo.com.br.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Buzaid
authors.affiliation: Temple University School of Medicine, St. Luke's Hospital & Health Network, Bethlehem, Philadelphia, USA.
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Agarwala
authors.affiliation: Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Hauschild
authors.affiliation: Georgetown-Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Atkins
keywords: Melanoma; chemotherapy; interleukin-2 (IL-2); ipilimumab; targeted therapy