detorubicin and Skin-Neoplasms

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.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Daunorubicin; Drug Evaluation; Electrocardiography; Female; Heart; Heart Diseases; Humans; Leukopenia; Lung Neoplasms; Lymphatic Metastasis; Male; Melanoma; Middle Aged; Myocardial Contraction; Skin Neoplasms; Stroke Volume; Thrombocytopenia

A 58-year-old man with subcutaneous metastases from a naevocarcinoma was prescribed 1 138 mg/m2 of a new anthracylic derivative, dietoxy-acetoxy-daunorubicine, at doses of 180 mg every three weeks. Irreversible cardiac failure occurred nine months after starting treatment, and was considered to be due to the toxic effects of the compound. He improved for a short period after very high doses of vasodilatators but death occured very shortly afterwards. Histological examination revealed severe subendocardial fibrosis, disseminated interstitial fibrosis, and degenerative and necrotic lesions of the myocytes. The authors discuss the factors involved in the cardiotoxicity of the anthracyclines: total dose, intervals between doses, associated risk, factors (age, radiotherapy). Even at usual doses signs of myocardial dysfunction are found in one third of patients treated, with the presence of histological lesions in all these cases, but clinical cardiac failure is rarely observed.

Topics: Cardiomyopathies; Daunorubicin; Heart Failure; Humans; Male; Melanoma; Middle Aged; Myocardium; Skin Neoplasms