Background: Intensification of post-remission therapy improves the cure rate of acute myeloid leukemia (AML) but is often accompanied by unacceptable toxicity. From 1985 to 1992 the Swiss Group for Clinical Cancer Research (SAKK) performed a randomized phase III trial to evaluate the effectiveness of one single postremission course of high-dose cytarabine (HDAC) in terms of leukaemia-free and overall survival in adults with cie novo AML. Patients and methods: Adult (15-65 years) AML patients in remission after two induction courses were randomly assigned to one consolidation course either with standard (SDAC: 100 mg/sqm 24 hours infusion over seven days) or with high-dose cytarabine (HDAC: 3000 mg/sqm every 12 hours as one-hour-infusion for six days). In addition, both arms included daunorubicin (45 mg/sqm daily on days 1 to 3). Thereafter, patients were observed without maintenance until relapse. Results: After two induction courses 208/276 eligible pa tients achieved remission (CR: 169, 61%, PR: 39, 14%), 41 were resistant (15%) and 20 died early (7%). Seventy-one patients in remission were not randomized. One hundred thirty-seven were randomized in CR/PR (67 SDAC, 70 HDAC). 4/70 patients randomized to HDAC did not receive it. Treatment-related mortality in HDAC was 1.4% (1/66). WHO grade 3-4 toxicities occurred in 14/67 SDAC and in 38/66 HDAC patients (P < 0.0001). The median event free survival was 10.8 (SDAC) vs. 12.2 months (HDAC; P = 0.18). The median overall survival was 24.6 (SDAC) vs. 32.6 months (HDAC; P = 0.07). Although statistically uncertain; HDAC reduced the hazard of progression (hazard ratio: 0.69, P = 0.08) and of death (hazard ratio: 0.70, P = 0.13). For 112 patients stratified as CR the estimated four-year disease-free survival was 25% (+/- 6%) with SDAC and 37% (+/- 6%) with HDAC (P = 0.09). The overall survival rates at four years were 38% (+7%) and 48% (+7%), respectively (P = 0.10). In multivariate analysis HDAC significantly reduced the hazard of relapse by 39% compared to SDAC (hazard ratio = 0.61, 95% CI: 0.37-0.99; P = 0.049). Conclusions: We conclude that early consolidation of adult AML in CR with a single course of HDAC is superior in terms of outcome to one cycle of SDAC. The results of our intensive, single course HDAC group compare favourably with less intensive, repetitive HDAC cycles, suggesting that Ara-C dose intensity may be more important than total dosage. In addition, our treatment strategy is much less toxic and less expensive.
