Background: Melphalan and prednisone (MP) has been the standard treatment for multiple myeloma (MM) for the last 30 years. Combination chemotherapy at conventional doses has not shown a significant prolongation of survival when compared to MP. There are few data comparing conventional chemotherapy at standard doses with conventional treatment at higher doses. We present the long-term outcome of 914 patients from two randomized trials comparing three different dose intensity regimens.Methods: From 1 January, 1985 to 31 December, 1989, 487 patients were randomized between MP (melphalan 9 mg/m2 p.o. and prednisone 60 mg/m2 days 1–4) and alternating VCMP (vincristine 1 mg i.v. on day 1, cyclophosphamide 500 mg/m2 i.v. on day 1, melphalan 6 mg/m2 p.o. on days 1–4, and prednisone 60 mg/m2 on days 1–4) and VBAP (vincristine 1 mg i.v. on day 1, BCNU and doxorubicin 30 mg/m2 i.v. each on day 1, and prednisone 60 mg/m2 on days 1–4). From 1 January, 1990 to 31 May, 1994, 427 patients were randomized between VCMP/VBAP at the above detailed doses (VCMP/VBAP ‘SD’) and the same regimen increasing the doses of cyclophosphamide and doxorubicin from 500 to 1200 mg/m2 and from 30 to 50 mg/m2, respectively (VCMP/VBAP ‘HD’).Results: Increasing dose intensity produced a significantly higher partial response rate (31% vs 45% vs 51% for MP, VCMP/VBAP ‘SD’, and VCMP/VBAP ‘HD’, respectively; P < 0.01). However, a significantly early death rate was observed in the HD arm (7.7, 7.5 and 12.1% for MP, VCMP/VBAP ‘SD’, and VCMP/VBAP ‘HD’, respectively; P = 0.05). Median duration of response (20 vs 18 vs 19 months for MP, VCMP/VBAP ‘SD’, and VCMP/VBAP ‘HD’, respectively; P = NS) and median survival (25 vs 31 vs 29 months for MP, VCMP/VBAP ‘SD’,... [ABSTRACT FROM AUTHOR]