Phase II Trial of Aclacinomycin in Acute Leukemia and Lymphosarcoma

Summary

A phase II trial of which preliminary results are available for 37 patients indicates that aclacinomycin applied in a continuous modality can induce complete or partial remissions in acute lymphoid leukemia resistant to all previously available drugs, and in lymphosarcoma. Bone marrow toxicity was the major side effect.

Daunorubicin (DRB) [1, 9] and adriamycin (ADM) [4] have been widely used, alone or in combinations [5], with remarkable oncostatic efficiency. In all conditions, however, their use has been limited because of two major side effects: (a) alopecia — some patients refuse to be exposed to a drug that suppresses hair growth; and (b) cardiotoxicity — although a given total dose has been calculated below which the myocardial risk is low [6], this risk is not nil and, in any case, the agent is generally not used beyond this total dose, which reduces its potential action.

Hence there is the considerable interest in other anthracyclines that have been considered to be less cardiotoxic and to cause less hair loss than ADM. We have systematically submitted all of them to a double test: electron-microscopic study of the myocardium and light-microscopic study of the skin of golden (cardiopathic) hamsters receiving three administrations per week of the dose corresponding (for mouse-hams- ter equivalence) to the optimally efficient dose, as far as survival is concerned, for murine L1210 leukemia [7]. The French detorubicin (DTR) [8,12,13] appears to be as cardiotoxic and to cause as much hair loss as ADM; the Italian 4’-epiadriamycin [3] is slightly less cardiotoxic, but causes the same hair loss as ADM; the American AD-32 [2] (N-trifluoroacetyl adriamycin-14-O-valerate) appears to be significantly less cardiotoxic and to induce no alopecia; the Japanese aclacinomycin (ACM) [11, 18] appears to be the least cardiotoxic and this preparation also induces no alopecia [7]

Hence, after the Japanese phase I trial in man [17], we started a phase II trial of aclacinomycin in man, the very preliminary results of which were reported in a short communication [16]. The results collected for the present meeting confirm the preliminary results.