title: Metastatic melanoma: a regional review and future directions.
abstract: OBJECTIVE
  . The incidence of malignant melanoma has risen steadily over recent decades. NCI data from 2005-2007 have suggested that 1.93% of individuals born today in the US will develop melanoma at some stage. Approximately 15% of patients with MM either present with metastatic disease or develop metastases during the course of their illness. Unfortunately, metastatic MM remains a challenge with limited treatment options, and median overall survival is 6-9 months.
  
  
  METHODS
  We reviewed our data for the treatment of metastatic MM over a period of four years. Data from all patients with metastatic MM treated with systemic therapy without clinical trials from 2006 to 2009 were reviewed. Response rate was determined as per RECIST criteria.
  
  
  RESULTS
  Sixty four patients were treated with one or more lines of cytotoxic therapy. Median age was 62 years (range, 23-82) with 53% males. Primary site of the disease was the skin in 75%, mucosal in 12.5%, ocular in 9.4% and nodal with an occult primary in 3.1%. Visceral metastases were present in 75% of patients at the start of treatment, including pulmonary (39.6%) and hepatic (34.4%). All patients were screened for brain metastases, which were present in 26.5% of patients. ECOG performance status was 0 in 7.8%, 1 in 68.7%, 2 in 9.4% and undocumented in the remaining 14%. Patients without brain metastases received single agent DTIC as first line; those with brain metastases received temozolomide. Response rate was 7% for DTIC and 28% for temozolomide, with median progression-free survival of 2.4 and 3.2 months, respectively. Seven patients who received DTIC are alive on follow-up, 2 have ongoing stable disease post-DTIC at 41 months and 18 months. Second line therapy with vinblastine was given to 21 patients (32%), with a response rate of 9.5% and median progression-free survival of 3.4 months. Median overall survival from initiation of therapy was 7.7 months for DTIC and 3.6 months for patients with brain metastases receiving temozolomide. A performance status of 2 was associated with shorter median overall survival (2.0 months).
  
  
  CONCLUSIONS
  . Our results are comparable to published data. Malignant melanoma is a disease with rising incidence and limited treatment options. These patients are best treated in the context of clinical trials as new targeted therapies are promising as future strategies.
authors.affiliation: Royal Marsden Hospital, London, UK. khurum.khan@icr.ac.uk
authors.forename: Khurum H
authors.initials: KH
authors.lastname: Khan
authors.forename: Rebecca B
authors.initials: RB
authors.lastname: Goody
authors.forename: Hassan
authors.initials: H
authors.lastname: Hameed
authors.forename: Awais
authors.initials: A
authors.lastname: Jalil
authors.forename: Vicky M
authors.initials: VM
authors.lastname: Coyle
authors.forename: James J A
authors.initials: JJ
authors.lastname: McAleer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000556:secondary; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000378:metabolism; D002986:Clinical Trials as Topic; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015994:Incidence; D007376:Interleukin-2 / Q000008:administration & dosage; D000074324:Ipilimumab; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000077204:Temozolomide; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D060908:CTLA-4 Antigen; D007376:Interleukin-2; D000074324:Ipilimumab; D014747:Vinblastine; D003606:Dacarbazine; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000077204:Temozolomide