Aclacinomycin A: clinical development of a novel anthracycline antibiotic in the haematological cancers.

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.