Phase I study of 4-demethoxydaunorubicin.
4-demethoxydaunorubicin (4-dm DNR), a new analog of daunorubicin, was tested at an every 3-week dose schedule in 63 evaluable patients with various forms of disseminated malignancy. Utilizing the intravenous (i.v.) route of administration, the maximum tolerated dose (MTD) was 15-18 mg/m2; with the oral route the MTD was 60 mg/m2. Myelosuppression represented the dose-limiting factor, and leukopenia was more often observed than thrombocytopenia. However, leukopenia was more frequently detected following i.v. administration while vomiting represented the most frequent toxic sign after oral administration. Loss of hair was moderate with either route of administration and comparatively less frequent and pronounced than that observed after doxorubicin (DX) and its analog 4'-epi-doxorubicin (4'-epi-DX). Aside from transient aspecific electrocardiographic changes recorded in 30% of patients, no cardiac toxicity was documented. Tumor response was documented in seven patients with malignant lymphomas, breast cancer, melanoma and carcinoma of uterine cervix. Two out of the seven responders achieved prolonged complete remission and four were resistant to doxorubicin. 4-dm DNR appears to be an analog worth further clinical trials.
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004064:Digestive System / Q000187:drug effects; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D015255:Idarubicin; D007275:Injections, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D013921:Thrombocytopenia / Q000139:chemically induced
D000970:Antineoplastic Agents; D015255:Idarubicin; D003630:Daunorubicin