title: Severe adverse events from the treatment of advanced melanoma: a systematic review of severe side effects associated with ipilimumab, vemurafenib, interferon alfa-2b, dacarbazine and interleukin-2.
abstract: BACKGROUND
  Current immunomodulatory agents for stage III and IV melanoma exert different mechanisms of action that manifest in distinct adverse events.
  
  
  OBJECTIVE
  This systematic review aims to synthesize safety data from clinical trials on ipilimumab, vemurafenib, interferon (IFN) alfa-2b, dacarbazine and interleukin (IL)-2 to elucidate the severe adverse events associated with each melanoma therapy.
  
  
  METHODS
  Through a systematic search using MEDLINE, EMBASE and the Cochrane Central Register between January 1, 2010 and June 1, 2012, we identified 32 clinical trials with 5802 subjects that met the inclusion criteria.
  
  
  RESULTS
  Ipilimumab was associated with immune-mediated diarrhea and colitis, with an incidence rate of 0.0017 cases per 100 person-years. Patients receiving vemurafenib developed keratoacanthomas and cutaneous squamous cell carcinoma at an incidence rate of 0.0025 cases per 100 person-years. Treatment with IFN alfa-2b precipitated depression at an incidence rate of 0.0002 cases per 100 person-years. Dacarbazine was associated with respiratory toxicity and dyspnea, with incidence rates of 0.0001 and 0.00008 cases per 100 person-years, respectively. IL-2 treatment induced vascular leak syndrome (VLS), with symptoms of hypotension and oliguria, was observed at incidence rates of 0.17 and 0.15 cases per 100 person-years, respectively. Findings may serve as a foundation for future research in this area and guide clinical recommendations.
authors.affiliation: Department of Dermatology, University of California Davis , Sacramento, CA , USA.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Ma
authors.forename: April W
authors.initials: AW
authors.lastname: Armstrong
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D003606:Dacarbazine / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects*; D007376:Interleukin-2 / Q000009:adverse effects*; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects; D012878:Skin Neoplasms / Q000188:drug therapy*; D013449:Sulfonamides / Q000009:adverse effects*; D000077484:Vemurafenib
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007211:Indoles; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D000074324:Ipilimumab; D011994:Recombinant Proteins; D013449:Sulfonamides; D000077484:Vemurafenib; D003606:Dacarbazine