Prognostic value of serum 5-S-cysteinyldopa for monitoring human metastatic melanoma during immunochemotherapy.

The melanin metabolite 5-S-cysteinyldopa (5-S-CD) has been reported to be helpful in detecting occult melanoma metastases and as a prognostic marker in B16 melanoma-bearing mice. The goal of our study was to analyze the significance of the serum 5-S-CD level for the biochemical detection of metastases in human malignant melanoma (MM) and for monitoring the progression or the immunochemotherapeutically induced regression of MM. From 11 patients with metastatic MM observed between 1991 and 1995, serum samples were collected before and after each cycle of immunotherapy or immunochemotherapy. Samples were analyzed for 5-S-CD by automated high performance liquid chromatography with electrochemical detection. Cycles of immunochemotherapy consisted of human interleukin 2 and IFN-alpha (four patients) or of human interleukin 2, IFN-alpha, and dacarbazine (seven patients). Serum value of 5-S-CD in our normal controls was 1.9 +/- 0.6 ng/ml. All patients with metastatic MM showed 5-S-CD serum levels above the upper normal limit of 3.2 ng/ml (10 nM) and ranged from 2.3-fold (4.3 +/- 3.9 ng/ml) of the normal control values in early stages of metastases to more than 50-fold (94.3 +/- 220.3 ng/ml) of the normal control values in advanced stages of the disease. In 28 of 41 (68%) immunochemotherapeutical cycles, a decrease of 5-S-CD was seen during therapy, and in 13 cycles (31.7%), an increase was seen. Patients with more than 68% decreasing cycles (defined as responders; n = 5) showed significantly longer survival times (P = 0.008) than patients with less than 68% decreasing cycles (nonresponders; n = 6). High levels of 5-S-CD were also observed in metastasizing amelanotic melanoma. Serum 5-S-CD is a useful marker for monitoring the clinical course of MM patients, for discriminating between responders and nonresponders to immunochemotherapy, and as a prognostic factor concerning survival time and death risk.