Systemic therapy of disseminated malignant melanoma: an evidence-based overview of the state-of-the-art in daily routine.
OBJECTIVE
In the metastatic stage, malignant melanoma is resistant to systemic treatment and carries a poor prognosis. A critical, evidence-based analysis of standard approaches based on an extended search of published literature and from different Internet sources is presented.


METHODS
A critical, evidence-based analysis of standard approaches and their variations to systemic therapy based on an extended search of published literature and from different Internet sources is presented. Few meta-analyses are available. Therefore, assessment of therapies is mainly based on randomized multicentre studies or clinical studies achieving an evidence level grade 1 or 2.


RESULTS
Monotherapy with DTIC (dacarbazine) is the standard. Based on overall survival data, polychemotherapies cannot be recommended. Combination of polychemotherapy with the cytokines interferon-alpha and interleukin-2 substantially augments chemotherapy induced response rates, but a meta-analysis for survival does not support its therapeutic superiority. Biological therapies such as vaccinations have not yet delivered results on a higher evidence level. Thus, immunotherapies as well as chemo-immunotherapies will have to be evaluated in further studies.


CONCLUSIONS
Although the therapeutic efficacy is very limited, dacarbazine cannot be rejected as standard therapy for disseminated melanoma, because no other therapeutic regimen exhibits a survival benefit over DTIC in an evidence-based analysis. This lack of therapeutic progress over the past 40 years clearly calls for further clinical studies, and patients should be enrolled into clinical trials whenever possible.
Nashan
D
D
Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany. dorothee.nashan@uniklinik-freiburg.de
Müller
M L
ML
Grabbe
S
S
Wustlich
S
S
Enk
A
A
D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019496:Cancer Vaccines; D003606:Dacarbazine / Q000627:therapeutic use*; D019317:Evidence-Based Medicine; D006801:Humans; D007167:Immunotherapy; D016898:Interferon-alpha / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D009362:Neoplasm Metastasis; D011379:Prognosis
D018906:Antineoplastic Agents, Alkylating; D019496:Cancer Vaccines; D016898:Interferon-alpha; D007376:Interleukin-2; D003606:Dacarbazine