DOSE INTENSIFICATION IN ACUTE MYLOID LEUKEMIA - GREATER EFFECTIVENESSAT LOWER COST, PRINCIPAL REPORT OF THE MEDICAL-RESEARCH COUNCILS AML9STUDY

Between 1984 and 1990, 972 patients aged 1-79 years with acute myeloid leukaemia (AML), from 85 British hospitals, were entered into the MRC 's 9th AML trial. Patients were randomized between DAT 1 + 5 (daunorub icin for 1 d, with cytarabine and 6-thioguanine for 5 d) and DAT 3 + 1 0 (same dose drugs for 3 and 10 d respectively) as induction therapy. The 63% who achieved complete remission (CR) were randomized to receiv e two courses of DAT 2 + 7 alternating with two courses of either MAZE (m-AMSA, 5-azacytidine, etoposide) or COAP (cyclophosphamide, vincris tine, cytarabine, prednisone). Finally, those still in CR were randomi zed to receive either 1 year of maintenance treatment with eight cours es of cytarabine and thioguanine followed by four courses of COAP, or no further cytotoxic therapy. Resistance to induction therapy was less common with the DAT 3 + 10 regimen than with DAT 1 + 5 (13% v 23%; P = 0.0001) and hence, despite a 5% increase in the risk of induction de ath, the CR rate was higher (66% v 61%; P = 0.15), Moreover, CR was ac hieved more rapidly with DAT 3 + 10 (median 34 v 46 d: P < 0.0001) and thus patients required less time in hospital (mean 20 v 29 d) and les s blood product support. 5-year relapse-free survival (28% v 23%; P = 0.05) and survival(23% v 18%; P < 0.05) were also better with DAT 3 10, Post-remission intensification of therapy with MAZE resulted in fe wer relapses (66% v 74% at 5 years; P = 0.03) but patients allocated M AZE required considerably more supportive care and 14 (4.5%) died foll owing 312 MAZE courses, whereas no deaths occurred following COAP. 5-y ear survival was not significantly higher with MAZE (37% v 31%). Final ly, although 1 year of out-patient maintenance treatment appeared to d elay, but not prevent, recurrence it did not improve 5-year survival w hich was non-significantly worse for those allocated maintenance treat ment (41% v 44%). We conclude that the more intensive induction regime n, DAT 3 + 10, is not only more effective than DAT 1 + 5, even for old er patients, but is also less expensive; intensive post-remission ther apy with MAZE achieves better leukaemic control but at the cost of sub stantial toxicity; whereas low-level maintenance therapy confers no ap parent advantage in survival as well as being inconvenient and costly.