A new methoxymorpholinyl derivative of
Adriamycin (ADR),
FCE 23762 (MRD), has recently been selected for phase I clinical trials for its reduced
cardiotoxicity and for its cytotoxic activity against a broad spectrum of solid
tumors and
leukemias that are sensitive or resistant to ADR. The purpose of the present study was to compare the in vitro antitumor activity of MRD and ADR on human
melanoma lines with different chemosensitivity to triazene compounds, among which
dacarbazine remains a reference
drug in the treatment of
melanoma. Both MRD and ADR were tested in vitro on three
melanoma lines, MI13443-MEL, SK-MEL-28, and M14, previously screened for their chemosensitivity to the triazene compound p-(3-methyl-1-triazeno)
benzoic acid,
potassium salt (
MTBA). The three lines were also analyzed for P-170 expression, total
glutathione (GSH) content, and GSH-related
enzyme activity. All
melanomas, whether sensitive or resistant to
MTBA, were susceptible to
anthracycline treatment. The cytotoxic activity of MRD was comparable with that of ADR, and no substantial difference was found in cell growth inhibition between the two drugs. When the relative chemosensitivity of the three lines was considered, SK-MEL-28 was found to be slightly less sensitive to MRD treatment than the other
tumors. This finding seems to correlate with the higher GSH-
peroxidase activity of this
melanoma relative to that of the MI13443 and M14 lines. These results show a homogeneous response of
melanoma lines to MRD treatment in vitro, suggesting that phase I clinical trials concerning this
drug, which in vivo appears to be activated to a more cytotoxic metabolite, could be extended to metastatic
melanomas, including those completely resistant to triazene compounds.