title: Brain metastasis in melanoma: clinical activity of CTLA-4 antibody therapy.
abstract: Melanoma metastasizes frequently to the brain, and brain metastases generally drive the prognosis of melanoma patients. Surgical and radiation therapy improve the outcome of selected melanoma patients with brain metastasis, while systemic treatment using cytotoxic agents still plays a limited role. Temozolomide and fotemustine are preferentially used in melanoma patients with brain metastases in the United States and in Europe, respectively, with modest clinical activity. However, the results obtained with either agent are still limited, and efforts are needed to improve the outcome of these patients who are generally excluded from clinical trials. Among therapeutic agents in development, antibodies that block the interaction of cytotoxic T-lymphocyte-associated antigen (CTLA-4) with its ligands B7.1 and B7.2 and thus enhance antitumor immune responses have shown clinical benefit in patients with metastatic melanoma, including durable control of brain metastases. This chapter reviews the current data and the rationale for ongoing and future trials of combination cytotoxic plus immunomodulatory therapy by US and Italian multicenter trial groups.
authors.affiliation: Medical Oncology, University of Washington, Seattle Cancer Care Alliance, Seattle, WA 98109-1023, USA. kmargoli@seattlecca.org
authors.forename: Kim A
authors.initials: KA
authors.lastname: Margolin
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Giacomo
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D015703:Antigens, CD / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary*; D060908:CTLA-4 Antigen; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D000074324:Ipilimumab; D007558:Italy; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary*; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000009:adverse effects; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D000077204:Temozolomide; D014481:United States
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D000074324:Ipilimumab; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D003606:Dacarbazine; C054368:fotemustine; D000077204:Temozolomide