A phase II trial of 200% ProMACE-CytaBOM-in patients with previously untreated aggressive lymphomas: Analysis of response, toxicity, and dose intensity

We showed in a phase I trial that the maximum tolerated dose of the ProMACE -CytaBOM regimen in patients with aggressive lymphoma was 200% (Gordon et a l, J Clin Oncol 14:1275, 1996). Based on these observations, we initiated a phase II trial designed to determine response, toxicity, and dose intensit y using this regimen. We analyzed 74 patients with advanced-stage (III or I V) or bulky stage II aggressive lymphoma. The overall complete response rat e was 69% (72% in evaluable patients). With a median follow-up of 4.5 years , the median survival has not yet been reached. The 4-year survival rate is 73% (95% confidence interval [CI] 62, 83%) and no difference was observed among International Prognostic Index (IPI) groups. The 4-year disease-free survival was 71% (95% CI 58, 84%) with no statistical difference between pa tients with IPI 0 to 1 versus 2 to 4. The toxicity was acceptable, though t he grade 4 hematologic toxicity rate for this regimen was 100%. Grade 4 non hematologic toxicity was 36%. Three cases of either myelodysplastic syndrom e or acute leukemia occurred at 7 months, 3.4 years, and 4.2 years after re gistration. Cytogenic analysis was available in two cases, showing inv(16) without French American British classification (FAB) M4 Po histology in one patient and a Bq-syndrome in the other. These data suggest that 200% ProMA CE-CytaBOM with either granulocyte-macrophage colony-stimulating factor (GM -CSF) or G-CSF results in a high complete remission rate and a disease-free survival comparable to any prior risk-based analysis in aggressive lymphom a. Before using this regimen in general practice, phase III clinical trials should be conducted. (C) 1999 by The American Society of Hematology.