Treatment of childhood acute myelogenous leukemia with an intensive regimen (AML-87) that individualizes etoposide and cytarabine dosages: short- andlong-term effects

The purpose of this study was to assess the feasibility and efficacy of a t reatment regimen for pediatric acute myelogenous leukemia (AML) that uses f our rotating drug pairs and adjusts dosages of etoposide and cytarabine to target specific plasma concentrations. Thirty-one girls and 27 boys (median age, 9.7 years) with de novo AML were treated on the protocol. Six cycles of chemotherapy were planned. Cycles 1 to 4 comprised the drug combinations cytarabine plus etoposide, cytarabine plus daunomycin, etoposide plus amsa crine, and etoposide plus azacitidine, respectively. For cycles 5 and 6, th e first two combinations were repeated. Dosages were adjusted to achieve pl asma concentrations of 1.0 mu M +/- 0.1 mu M cytarabine and 30 mu M +/- 0.3 mu M etoposide. Forty-four patients (76%) entered complete remission. Of t hose, 24 have had relapses; 23 remain alive in first or subsequent remissio n. The 5-year event-free survival (EFS) estimate was 31.0% +/- 5.9%; the 5- year survival estimate was 41.4% +/- 6.3%. Six patients (10%) died of the t oxic effects of therapy. Severe neutropenia occurred in all cycles. Long-te rm complications of therapy included hepatitis C, cardiac insufficiency, an d hearing loss. Adjustment of cytarabine and etoposide dosage was feasible for achieving targeted plasma drug concentrations; however, the potential c linical efficacy of this approach was offset by substantial acute and long- term toxicity.