detorubicin and Melanoma

51 patients with malignant melanomas who had not previously received chemotherapy were studied in a phase III trial. They were all advanced cases, either in relapse or showing metastatic spread and with one or several measurable tumor sites. They were judged to be too advanced for surgery or radiotherapy. They were split at random into two groups. Both groups received DTIC (250 mg/m2, IV, over 4 days every three weeks) and one group received detorubicin (120 mg/m2, IV every three weeks) as well. Detorubicin is a new anthracyclin drug which has shown promise in the treatment of these tumors in a previous trial. The combination of the two drugs produced better results than dacarbazine alone. Eight 50% regressions were obtained out of 22 cases studied (36%) with the combination, as opposed to 4 out of 26 (15%) with the single drug. The average length of response was also longer for the combination, i.e. 6 months opposed to 5 for the single drug. The differences were not, however, statistically significant (X2 = 2.09). Toxic reactions were also more frequent with the combination therapy (65%) than with DTIC alone (40%) (X2 = 0.42), as well as more serious because of the myocardial toxicity of the anthracyclin drug. This trial showed that a combination of dacarbazine with detorubicin improves the therapeutic outcome. Whether this represents a real benefit will need statistical confirmation from trials of combinations using other anthracyclins.

Topics: Adult; Aged; Clinical Trials as Topic; Dacarbazine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Male; Melanoma; Middle Aged; Time Factors

Several new investigational agents have shown some promise in the treatment of patients with disseminated melanoma. While earlier studies of combination chemotherapy led to increased toxicity without improved anti-tumor effect, more recent combination regimens have produced responses up to 50%. One of these is a dose-intensification regimen using high-dose cisplatin and the chemoprotective drug WR-2721. Other treatments under study include autologous bone marrow transplantation plus thiotepa, a combination regimen of chemotherapy and interferon, and newer agents such as taxol, tauromustine, and detrorubicin.

Topics: Alkaloids; Amifostine; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Carmustine; Cisplatin; Cyclophosphamide; Dacarbazine; Daunorubicin; Humans; Lomustine; Melanoma; Nitrosourea Compounds; Paclitaxel; Procarbazine; Tamoxifen; Taurine; Thiotepa; Vincristine; Vindesine

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 phase II trial of detorubicin (DTR) has been conducted on 164 patinets with solid tumors. Regressions greater than or equal to 50% were obtained in 23% of breast carcinoma patients, in 17% of head and neck carcinoma patients and of melanoma patients, and in 6% of ureri cervic carcinoma patients. DTR seems as toxic as adriamycin on bone marrow and the heart and might induce a little less alopecia.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Carcinoma; Daunorubicin; Dose-Response Relationship, Drug; Drug Evaluation; Female; Head and Neck Neoplasms; Humans; Male; Melanoma; Middle Aged; Neoplasms; Uterine Neoplasms

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