carubicin and Leukemia

Topics: Aclarubicin; Anthraquinones; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Cell Survival; Daunorubicin; Doxorubicin; Drug Evaluation; Epirubicin; Heart; Humans; Idarubicin; Leukemia; Menogaril; Mitoxantrone; Naphthacenes; Nogalamycin; Sarcoma; Structure-Activity Relationship

Topics: Aclarubicin; Animals; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Daunorubicin; Doxorubicin; Female; Glycosides; Hodgkin Disease; Humans; Leukemia; Lung Neoplasms; Lymphoma; Naphthacenes; Ovarian Neoplasms; Sarcoma

Topics: Adult; Animals; Antibiotics, Antineoplastic; Carubicin; Chemical Phenomena; Chemistry; Child; Dogs; Humans; Leukemia; Leukemia L1210; Lymphoma; Mice; Rats; Sarcoma

The clinical trials of karminomycin, a new Soviet antitumor antibiotic in treatment of different malignant tumors showed that the drug had a pronounced antitumor activity against the soft tissue sarcomas of various histogenesis, lympho- and reticulosarcoma, acute leukemia and some other neoplasms.

Topics: Adolescent; Antibiotics, Antineoplastic; Carubicin; Clinical Trials as Topic; Drug Evaluation; Humans; Leukemia; Male; Middle Aged; Neoplasms; Remission, Spontaneous; USSR

The new hydrophilic derivatives of 14-hydroxycarminomycin were obtained using 13-dimethyl ketal of 14-bromocarminomycin (6) as the starting compound. The reductive alkylation of 6 with melibiose or D-galactose followed by hydrolysis of the corresponding intermediate bromoketals 9 and 11 produced 3'-N-[-alpha-D-(galactopyranosyl-(1 --> 6)-O-D-1-desoxyglucit-1-yl]-14-hydroxycarminomycin (10) and 3'-N-(1-desoxy-D-galactit-1-yl)-14-hydroxycarminomycin (12), respectively. These novel derivatives 10 and 12 were less toxic than carminomycin or 14-hydroxycarminomycin for leukemia (K562) and breast carcinoma (MCF-7) cells. Importantly, carminomycin, 14-hydroxycarminomycin and compounds 10 and 12 were similarly active for wild type cells and their multidrug resistant (MDR) sublines, K562i/S9 and MCF-7Dox.

Topics: Antibiotics, Antineoplastic; ATP Binding Cassette Transporter, Subfamily B; Breast Neoplasms; Carubicin; Cell Survival; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Female; Genes, MDR; Humans; Leukemia; Structure-Activity Relationship; Tumor Cells, Cultured

Twenty courses of carminomycin were administered to 18 evaluable adult patients with acute leukemia (14 ANLL, 2 ALL, 2 CGL-BC). All but one received daily doses of 6-14 mg/m2 for 5 consecutive days. Two patients older than 60 yr had not prior chemotherapy and the others had refractory or relapsed disease. The median age was 60 yr. Three ANLL patients achieved complete remission for 8, 9 and 9 months respectively, with no maintenance therapy. None of these had proven clinical resistance to daunomycin and/or doxorubicin. Mucositis was dose-related and dose-limiting. Nausea and vomiting were rare. Alopecia was constant. Cardiac arrythmia was ascribed to carminomycin in two patients. One episode of cardiac failure seemed clearly drug-related and recovered with symptomatic treatment. In conclusion, encouraging antileukemic activity was observed with carminomycin in poor-risk patients. At doses up to 12 mg/m2 day X 5, extramedullary toxicity remained acceptable.

Topics: Acute Disease; Adult; Aged; Carubicin; Daunorubicin; Drug Evaluation; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged

Future studies with daunorubicin involve mainly comparative evaluations with other anthracycline antibiotics and related compounds. Efforts are ongoing to improve the therapeutic index of these drugs. This includes not only laboratory development but also clinical evaluation of analogs, manipulations in dose schedules, and the use of protectors of toxic manifestations, primarily of cardiomyopathy. Technological advances in the clinical area permit, for example, the exploration of daunorubicin and related compounds by continuous infusion under more precise pharmacologic and cardiologic monitoring than was possible when they were initially introduced.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Carubicin; Child; Daunorubicin; Doxorubicin; Drug Evaluation; Humans; Leukemia; Naphthacenes; Structure-Activity Relationship

The intracellular distribution of important chemotherapeutic antibiotics belonging to the anthracycline group (e.g. adriamycin) can be detected by laser flow cytometry. The indirect method is based on the interference of these compounds with the binding of propidium iodide to the nuclear DNA. While in the direct method, the intracellular fluorescence of these antibiotics is excited and detected with a laser beam in a flow system. The present report demonstrates the use of these two methods for intracellular detection and quantitation of a number of important anthracyclines.

Topics: Animals; Antibiotics, Antineoplastic; Carubicin; Cell Line; Cytological Techniques; Daunorubicin; DNA; Doxorubicin; Humans; Lasers; Leukemia; Mice; Nogalamycin; Propidium; Spectrometry, Fluorescence