aclarubicin and Cardiomyopathies

Doxorubicin is an essential component of the treatment of aggressive lymphoma, childhood solid tumors, bone and soft tissue sarcomas, and breast cancer and additional indications are emerging. On the other hand, daunorubicin has occupied the central position of interest in the treatment of acute leukemia. Epirubicin has a spectrum very similar to doxorubicin but lesser toxicity. The ability to protect against cardiotoxicity with ICRF-187 further enhances clinical interest in exploiting modifications in doze intensity to therapeutic advantage. Idarubicin has at least equivalent activity to daunorubicin and doxorubicin in leukemia. New areas of research in relation to anthracycline antibiotics include introduction of new the analogs, insight into mechanisms of resistance, the reversal of multidrug resistance in vitro, the protection of cardiac toxicity, and the study of other important biochemical reactions relevant to cytotoxicity. Orally active anthracyclines such as idarubicin and compounds which lack cross-resistance with the parent drugs or have other mechanisms for cytotoxicity are being developed. It is likely that these modifications will lead to an expanding therapeutic spectrum for these already widely useful drugs.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Cardiomyopathies; Carubicin; Doxorubicin; Drug Resistance; Epirubicin; Humans; Idarubicin; Menogaril; Molecular Structure; Neoplasms; Nogalamycin

Doxorubicin is an essential component of the treatment of aggressive lymphoma, childhood solid tumors, bone and soft tissue sarcomas, and breast cancer and additional indications are emerging. On the other hand, daunorubicin has occupied the central position of interest in the treatment of acute leukemia. Epirubicin has a spectrum very similar to doxorubicin but lesser toxicity. The ability to protect against cardiotoxicity with ICRF-187 further enhances clinical interest in exploiting modifications in doze intensity to therapeutic advantage. Idarubicin has at least equivalent activity to daunorubicin and doxorubicin in leukemia. New areas of research in relation to anthracycline antibiotics include introduction of new the analogs, insight into mechanisms of resistance, the reversal of multidrug resistance in vitro, the protection of cardiac toxicity, and the study of other important biochemical reactions relevant to cytotoxicity. Orally active anthracyclines such as idarubicin and compounds which lack cross-resistance with the parent drugs or have other mechanisms for cytotoxicity are being developed. It is likely that these modifications will lead to an expanding therapeutic spectrum for these already widely useful drugs.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Cardiomyopathies; Carubicin; Doxorubicin; Drug Resistance; Epirubicin; Humans; Idarubicin; Menogaril; Molecular Structure; Neoplasms; Nogalamycin

The efficacy and safety of a modified CAG (low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor) regimen with an increased aclarubicin dosage [high-dose (HD)-CAG] were observed in 145 patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and compared to the results of 172 patients treated with a conventional CAG regimen. The HD-CAG regimen showed both a higher complete remission (CR) rate (60.7% vs. 46.5%, P=0.013) and overall response (OR) rate (74.5% vs. 63.4%, P=0.039) than CAG. For patients aged <60 years, HD-CAG manifested an efficacy advantage over the CAG regimen (62.6% vs. 47.4%, P=0.015). The 4-year overall survival (OS) rate was 30.3%±13.2% with a median survival time of 19.0±5.4 months for patients re-induced with the HD-CAG regimen, which showed no significant difference compared to the CAG regimen (with a 4-year OS rate of 18.2%±5.3% and a median survival time of 16.0±3.6 months, P=0.485). The main adverse effect was myelosuppression; platelet recovery over 50×10(9)/L was extended by the HD-CAG regimen (15 days vs. 10 days of the CAG regimen, P=0.003), which was tolerable and manageable. HD-CAG can safely improve efficacy compared to the CAG regimen and thus serves as an alternative treatment for R/R AML.

Topics: Aclarubicin; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Cardiomyopathies; Chemical and Drug Induced Liver Injury; Cytarabine; Dose-Response Relationship, Drug; Female; Granulocyte Colony-Stimulating Factor; Humans; Kaplan-Meier Estimate; Kidney Diseases; Leukemia, Myeloid, Acute; Male; Middle Aged; Proportional Hazards Models; Recurrence; Remission Induction; Retrospective Studies; Salvage Therapy; Treatment Outcome; Young Adult

The hearts of 16 autopsy cases with a past history of administration of anthracycline antitumor drugs (DNR, ADR and ACM) and a sign of cardiac failure were investigated morphologically. In macroscopic observation, both ventricles were more or less dilated with thinning of the ventricular wall. Mural thrombi were recognized in the left ventricle of 2 cases. Histologically, the myocardial lesions could be roughly classified into two groups, a) myocardial changes in cases with rapidly developed cardiac failure (acute form), and b) myocardial changes in cases with relatively slowly developed cardiac failure. In acute form, myocardial cells showed marked swelling with dilatation of central sarcoplasmic core, marked reduction of myofibrils, vacuolization of cytoplasm and enlargement of nucleus accompanied by distinct large nucleolus. Necrotic myocardial cells were scattered among these degenerative cells. These degenerative and necrotic cells were distributed diffusely in both ventricular walls, but were more frequent in the left ventricular wall than in the right one. Inflammatory cell infiltration was also recognized not only in the myocardium, but also in the endocardium and epicardium. In chronic form, on the other hand, atrophy and attenuation of myocardial cells with a hypereosinophilic change of the cytoplasm and an increase in number of brown pigments, and marked reduction of myocardial cells were most common findings. These changes of chronic form, however, could not be identified as the specific changes of anthracycline cardiotoxicity. Fibrosis was hardly seen in the myocardium of both acute and chronic forms.

Topics: Aclarubicin; Adult; Aged; Antibiotics, Antineoplastic; Cardiomyopathies; Daunorubicin; Doxorubicin; Female; Humans; Male; Middle Aged; Myocardium; Naphthacenes

Adriamycin (ADM) is a very effective antimitotic agent but its use is limited by its cardiotoxicity. New anthracycline drugs such as aclacinomycin A (ACMA) have been developed and have to be compared with ADM after chronic experimental intoxication. Three groups of randomised rats were compared: the ADM group receiving 2 mg/kg/week X 13 by intraperitoneal injection; the ACMA group receiving 4 mg/kg/week X 13 and a control group: 7 rats. The rats were autopsied at the 20th week. The heart was stopped in diastole and fixed by aortic retroinfusion of glutaraldehide for electronic microscopy (EM). In the ADM group, mean weight fell from the 4th week and mortality was 11/16 at 20 weeks. Voluminous haemorrhagic ascites was associated with peritoneal fibrosis in 12/16. Cardiac failure was observed in 4 cases but on light microscopy (LM) myofibril degeneration was constant and focal without sarcoplasmic reticulum or mitochondrial changes on EM. In the ACMA group the loss of weight occurred at 10 weeks and mortality due to toxicity was nil. There was no cardiac failure; myocytolysis was absent on LM and slight in 4/13 cases on EM with a moderate dilatation of the sarcoplasmic recticulum and presence of numerous residual bodies in the striated skeletal fibres in 5/15 cases. In this study, the ACMA had very little cardio and general toxicity in comparison with ADM. The technique of fixing the heart by retrograde infusion prevents, as far as possible, artefacts on EM affecting mainly the mitochondria.

Topics: Aclarubicin; Animals; Body Weight; Cardiomyopathies; Doxorubicin; Male; Myocardium; Naphthacenes; Random Allocation; Rats

Topics: Aclarubicin; Animals; Cardiomyopathies; Cricetinae; Doxorubicin; Heart; Male; Mesocricetus; Microscopy, Electron; Myocardium; Naphthacenes; Rabbits