A phase II study of
detorubicin, the semisynthetic 14-diethoxyacetoxy
ester of
daunorubicin, was conducted in 42 patients with metastatic
melanoma. The
drug was administered in a dose range of 120 to 180 mg/m2 and repeated at 3-week intervals. One clinical complete remission (soft tissue) and seven partial responses (three visceral and four soft tissue) were observed among the 22 patients who had undergone no prior
chemotherapy, a complete and partial response rate of 36%. The duration of response varied from 2 to 27 months with a median of 10 months. There were also four (19%) minor responses (one visceral and three soft tissue). In contrast, among the 20 patients who had undergone prior
chemotherapy treatment, only three patients showed a minor response. General toxicities were acceptable and were similar to those of
Adriamycin (Adria Laboratories, Columbus, Ohio).
Cardiac toxicity was evaluated by cardiac biopsy and
radionuclide scan. Cardiac biopsy changes were identical to those observed with
Adriamycin and were progressive with cumulative dose. One patient had a high-grade biopsy at a cumulative
detorubicin dose of 1,420 mg/m2. Similarly, a trend of decreasing ejection fraction with cumulative dose was noted. Only one patient developed
congestive heart failure at a cumulative dose of 1,290 mg/m2, that was well compensated with
digoxin and
diuretics. In contrast to
Adriamycin,
detorubicin has shown activity in previously untreated patients with metastatic
melanoma.