aclarubicin and Arrhythmias--Cardiac

Aclacinomycin A (aclarubicin; ACM) is a new class II anthracycline antibiotic. Preclinical studies suggested that ACM had approximately equivalent antitumour activity but produced substantially less cardiotoxicity compared to other anthracyclines. Because of the recognized importance of these compounds in the treatment of haematological tumours, clinical trials of ACM were initiated in the late 1970s. ACM has been extensively evaluated in patients with relapsed leukaemia and advanced malignant lymphoma. Analysis of results compiled from Europe, Japan, and the United States shows that ACM is probably equivalent to doxorubicin for remission induction of patients with relapsed acute non-lymphoblastic leukaemia. Initial studies using ACM alone and in combination with standard cytotoxic drugs in previously untreated patients compare favourably with the best standard treatment for this disease. The antitumour activity of ACM in patients with acute lymphoblastic leukaemia or malignant lymphoma who have previously received doxorubicin or daunorubicin is low, and the issue of whether ACM lacks clinical cross-resistance to other anthracyclines is unresolved. Acute cardiac arrhythmias have been observed following administration of ACM, but congestive cardiomyopathy has been uncommon. Results to date all indicate that ACM has fulfilled its early expectations of antileukaemic activity and reduced toxicity. These hypotheses should now be evaluated in prospective, randomized trials with conventional anthracyclines.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Arrhythmias, Cardiac; Clinical Trials as Topic; Drug Evaluation; Drug Evaluation, Preclinical; Drug Resistance; Heart; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Naphthacenes

Aclacinomycin A (aclarubicin; ACM) is a new class II anthracycline antibiotic. Preclinical studies suggested that ACM had approximately equivalent antitumour activity but produced substantially less cardiotoxicity compared to other anthracyclines. Because of the recognized importance of these compounds in the treatment of haematological tumours, clinical trials of ACM were initiated in the late 1970s. ACM has been extensively evaluated in patients with relapsed leukaemia and advanced malignant lymphoma. Analysis of results compiled from Europe, Japan, and the United States shows that ACM is probably equivalent to doxorubicin for remission induction of patients with relapsed acute non-lymphoblastic leukaemia. Initial studies using ACM alone and in combination with standard cytotoxic drugs in previously untreated patients compare favourably with the best standard treatment for this disease. The antitumour activity of ACM in patients with acute lymphoblastic leukaemia or malignant lymphoma who have previously received doxorubicin or daunorubicin is low, and the issue of whether ACM lacks clinical cross-resistance to other anthracyclines is unresolved. Acute cardiac arrhythmias have been observed following administration of ACM, but congestive cardiomyopathy has been uncommon. Results to date all indicate that ACM has fulfilled its early expectations of antileukaemic activity and reduced toxicity. These hypotheses should now be evaluated in prospective, randomized trials with conventional anthracyclines.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Arrhythmias, Cardiac; Clinical Trials as Topic; Drug Evaluation; Drug Evaluation, Preclinical; Drug Resistance; Heart; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Naphthacenes

A patient with myelocytic leukemia who showed electrical alternans of the T-U wave with no change in the QRS complex following chemotherapy is described. Electrocardiogram taken 4 days later showed ventricular quadrigeminy in which the T-U wave of the first sinus beat after the ventricular premature contraction was markedly less prominent compared to the successive two sinus beats which showed marked prolongation and inverted T-U waves. The causative factors for alternans of T-U waves may include hypochloremic alkalosis with hypopotassemia and myocardial damage by anticancer drugs such as daunomycin and aclarubicin chloride used for the underlying disease.

Topics: Aclarubicin; Antineoplastic Combined Chemotherapy Protocols; Arrhythmias, Cardiac; Cytarabine; Daunorubicin; Electrocardiography; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged

Nine patients with acute non lymphoblastic leukaemia (ANLL) were treated with Aclacinomycin in the doses of 20 mg/m2/day x 7 days in 30' lasting intravenous infusion and Cytosin arabinosid 100 mg/m2/day x 7 days in continuous infusion as well as control group consisted of 30 healthy people were examined by means of 24 hrs Holter ECG monitoring and ultrasonocardiography (UCG) to evaluate the influence of Aclacinomycin A (Aclaplastin - Behring) on cardiac rhythm and function. The UCG and Holter examinations were performed before Aclacinomycin and after 7-10 days from the beginning of the therapy. There were no statistical differences between the results of UCG examination in Aclacinomycin-treated group before the therapy and the control group. A slight nonsignificant decrease in left ventricular stroke volume and ejection fraction were observed after Aclacinomycin. Cardiac index decreased after the therapy (p less than 0.05) but was of normal value. The only true significant (p less than 0.001) decrease was observed in the contractility of cardiac fibres but the cardiac failure was not observed. No alterations in left ventricular posterior wall and intraventricular septum thickness were found. The effusion to pericardium was observed in 2 pts in the initial study and in 1 of them also after the therapy. The obtained results supported the clinical observations that Aclacinomycin A is promising agent for the treatment of ANLL because of its low cardiotoxicity.

Topics: Aclarubicin; Adult; Arrhythmias, Cardiac; Cytarabine; Electrocardiography; Female; Humans; Infusions, Intravenous; Leukemia, Myeloid, Acute; Male

Aclacinomycin A (ACM-A), an anthracycline analog, was given to 17 patients with solid tumors and to one patient with multiple myeloma, in a phase I clinical trial. A single dose of 60-120 mg/m2 was given every 3 weeks. Dose-limiting toxicity was myelosuppression, especially thrombocytopenia. Granulocytopenia was variable and did not always recover by Day 21 in time for the next ACM-A treatment. Other toxic effects were nausea, vomiting, urticaria, and elevation of hepatic enzymes. Alopecia was not a side effect, even in patients receiving multiple courses of ACM-A. Nine patients were monitored with 24-hour continuous ECG recordings (Holter) on 19 ACM-A treatment days. The incidence of premature atrial and ventricular beats was significantly increased following ACM-A administration. In addition, one patient developed episodes of high-degree atrioventricular block and complete heart block after each of four ACM-A doses, necessitating the insertion of a pacemaker. No antitumor responses were seen in the ten patients who had measurable disease and who had received two or more courses of ACM-A. The recommended doses for solid tumor phase II studies are 100 mg/m2 as a single dose every 4 weeks for patients with high performance status and minimal prior chemotherapy and 60 mg/m2 every 4 weeks for all other patients. Until the acute cardiac effects of ACM-A are further understood, we recommend that all patients receiving ACM-A be monitored by ECG recordings.

Topics: Aclarubicin; Adult; Aged; Antibiotics, Antineoplastic; Arrhythmias, Cardiac; Blood Cells; Drug Evaluation; Female; Humans; Male; Middle Aged; Naphthacenes; Neoplasms