The prognosis of patients with metastatic
melanoma remains poor. In patients with distant
metastases only low response rates between 10% and 15% have been achieved by the most effective
cytostatics in single-agent
therapy leading to a mean 5-year survival rate of less than 5%. More aggressive treatment regimens using multidrug
chemotherapy yielded response rates of up to 40% but failed to show a significant benefit in overall survival compared to single-agent
therapy. However, complete remissions of metastatic lesions after multidrug
cytostatic regimens have been reported in some cases of
melanoma patients. To evaluate an in vitro test system providing information on the
drug sensitivity profile of
melanoma cells, we examined
tumor tissue specimens from 31 metastatic
melanoma patients with an
ATP-based chemosensitivity assay (
ATP-TCA) testing eight anticancer drugs alone or in different combinations. Chemosensitivity was assessed using a
luciferin-
luciferase- based luminescence assay providing individual chemosensitivity indices for each test
drug. We found a heterogeneous chemosensitivity in the
melanoma tissue samples tested. The highest sensitivity was detected for the combination of
treosulfan and
gemcitabine, with 76% of the tissue samples revealing high sensitivity and 10% resistance, followed by the combination of
paclitaxel and doxorubicine (66%/0%),
gemcitabine and
cisplatin (55%/21%),and
paclitaxel and
cisplatin (46%/8%). Our data indicate that the
ATP-TCA can be used to select patients who might benefit from an individually adapted
cytostatic therapy. On the basis of these results a multicenter trial has recently been initiated to evaluate the feasibility and predictive value of an
ATP-TCA directed
chemotherapy in metastatic
melanoma patients.