carubicin and marcellomycin

This review describes the current clinical results of phase I and II trials of new antitumor drugs such as the new anthracyclines: epirubicin, idarubicin, esorubicin, carminomycin and marcellomycin; the second generation cisplatin: carboplantin, CHIP, TNO-6, DACCP and JM-40; mitoxantrone, AMSA, AZQ, Tiazofurin, DFMO and others.

Topics: Aminoacridines; Amsacrine; Anthracyclines; Anthraquinones; Antibiotics, Antineoplastic; Antineoplastic Agents; Aziridines; Benzoquinones; Carboplatin; Carubicin; Cisplatin; Daunorubicin; Doxorubicin; Eflornithine; Epirubicin; Humans; Idarubicin; Mitoxantrone; Naphthacenes; Neoplasms; Organoplatinum Compounds; Ornithine; Ribavirin

The sensitivity of bone marrow granulocyte-macrophage colony-forming cells to 4 anthracyclines, carminomycin, marcellomycin, aclacinomycin A, and N,N-dibenzyldaunorubicin, was studied using the agar diffusion chamber technique which allows exposure of target cells to drug metabolized by the chamber-bearing host after i.v. injection. Colony-forming cells from mice, dogs, and humans were all found to have exponential dose-response curves for the agents studied, with variation of the slopes between species and agents. Species sensitivities as determined by the assay related well to the available toxicological and clinical data for specific drugs. The rank order of sensitivity of human marrow colony-forming cells to five anthracyclines tested in this and a previous study related very closely to doses producing moderate leukopenia in Phase I and II clinical studies. A dose of 200 mg/sq m of N,N-dibenzyldaunorubicin would be expected to produce moderate leukopenia in future clinical trials. This assay may be useful in predicting human bone marrow toxicity of new agents before actual clinical trial because of the ability to study the survival of human colony-forming cells directly.

Topics: Aclarubicin; Animals; Anthracyclines; Antibiotics, Antineoplastic; Carubicin; Daunorubicin; Dogs; Dose-Response Relationship, Drug; Female; Hematopoietic Stem Cells; Male; Mice; Naphthacenes; Species Specificity

Topics: Aclarubicin; Anthracyclines; Antibiotics, Antineoplastic; Bleomycin; Carubicin; Centrifugation, Density Gradient; Daunorubicin; Diffusion; DNA, Circular; Doxorubicin; Drug Interactions; Electrophoresis, Agar Gel; Molecular Conformation; Naphthacenes

The kinetics of cellular and nuclear incorporation of a number of new anthracyclines into daunorubicin-sensitive and -resistant Ehrlich ascites cells were determined in vitro. For comparative quantitative analyses the substances were extracted with a 0.3 N HCl/50% ethanol (v/v) solution from either whole cells or purified citric acid nuclei after various intervals of in vitro incubation. At steady state the intracellular and intranuclear concentrations of daunorubicin and doxorubicin were reduced by about 50% in the resistant cell line. Marcellomycin and carminomycin concentrations were only reduced by 9% and 11%, respectively, and no differences between sensitive and resistant cells were seen in the case of aclacinomycin A and AD 32. When the ratios of nuclear to cellular drug were determined at steady state lowest value was found for AD 32 (0.26). In contrast, aclacinomycin A and carminomycin were mainly (78% and 74%) and marcellomycin almost exclusively (95%) concentrated in the nucleus. When the total amounts of drug incorporated per cell were compared, the highest values were measured for aclacinomycin A and the lowest for AD 32 both in the sensitive and the resistant tumor. Additional determinations of the 50% inhibitory concentrations for thymidine uptake showed similar differences between these anthracyclines which were not related to the potency of the drugs in vivo. It is concluded that apart from nuclear incorporation and inhibition of DNA synthesis other factors may be decisive for anthracycline-induced cytotoxicity.

Topics: Aclarubicin; Animals; Anthracyclines; Antibiotics, Antineoplastic; Carcinoma, Ehrlich Tumor; Carubicin; Cell Nucleus; Daunorubicin; DNA, Neoplasm; Doxorubicin; Drug Resistance; Female; In Vitro Techniques; Mice; Naphthacenes