title: A phase II trial of 200% ProMACE-CytaBOM in patients with previously untreated aggressive lymphomas: analysis of response, toxicity, and dose intensity.
abstract: 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 al, J Clin Oncol 14:1275, 1996). Based on these observations, we initiated a phase II trial designed to determine response, toxicity, and dose intensity using this regimen. We analyzed 74 patients with advanced-stage (III or IV) or bulky stage II aggressive lymphoma. The overall complete response rate 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 patients with IPI 0 to 1 versus 2 to 4. The toxicity was acceptable, though the grade 4 hematologic toxicity rate for this regimen was 100%. Grade 4 nonhematologic toxicity was 36%. Three cases of either myelodysplastic syndrome or acute leukemia occurred at 7 months, 3.4 years, and 4.2 years after registration. Cytogenic analysis was available in two cases, showing inv(16) without French American British classification (FAB) M4 EO histology in one patient and a 5q-syndrome in the other. These data suggest that 200% ProMACE-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 lymphoma. Before using this regimen in general practice, phase III clinical trials should be conducted.
authors.affiliation: Northwestern University Medical School, Chicago, IL 60611-3008, USA.
authors.forename: L I
authors.initials: LI
authors.lastname: Gordon
authors.forename: M
authors.initials: M
authors.lastname: Young
authors.forename: E
authors.initials: E
authors.lastname: Weller
authors.forename: T M
authors.initials: TM
authors.lastname: Habermann
authors.forename: J N
authors.initials: JN
authors.lastname: Winter
authors.forename: J
authors.initials: J
authors.lastname: Glick
authors.forename: C
authors.initials: C
authors.lastname: Ghosh
authors.forename: P
authors.initials: P
authors.lastname: Flynn
authors.forename: P A
authors.initials: PA
authors.lastname: Cassileth
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D003561:Cytarabine; D001761:Bleomycin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate