Clinical trials in disseminated malignant melanoma

At present the available treatment modalities are not therapeutic for disseminated stage III- and IV melanoma. The management of these patients therefore concentrates primarily on effective palliation taking care to improve the quality of life. As an exception from this rule, patients with regional or solitary metastases may be treated vigorously to improve survival: However, (a) regional tumor resection with or without radiotherapy; (b) regional perfusion of tumor-bearing extremities, and (c) indicator chemotherapy, followed by the resection of solitary metastases and sometimes secondary adjuvant treatment with the same cytostatic regimen, will cure only about 20% of these patients. Systemic treatment with cytostatic agents given alone or in combination fail to reproducibly reach an objective remission rate of more than 20% or a gain in median survival of more than 6 months. The addition of biomodulators may even worsen these results and endocrine treatments are rarely helpful. Current research therefore concentrates on defining a well selected patient population with skin-, soft tissues-, and lung-metastases, who will benefit from systemic treatment, as well as on the development of drug derivatives with fewer side effects. Another small step forward may be expected from sophisticated techniques such as linking cytotoxins to monoclonal antibodies for selective cell killing, or rendering tumor cell membranes vulnerable to endogenous and/or exogenous attacks by altering their structure with the help of biomodulators (Interferons, DNCB etc.), or priming lymphokine-activated killer cells for specific lysis of vital tumor-associated antigens. Melanoma remains the cornerstone for testing the efficiency of medical oncology in general.