title: A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype.
abstract: BACKGROUND
  A phase II trial of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) from the National Cancer Institute showed promising activity in untreated diffuse large B-cell lymphoma. The Cancer and Leukemia Group B conducted a study to determine if these results could be reproduced in a multi-institutional setting.
  
  
  METHODS
  The study included 69 patients with untreated diffuse large B-cell lymphoma at least 18 years of age and at least stage II. Radiaton therapy was not permitted on study. Median age was 58 years (range 23-83) and 40% had high-intermediate or high International Prognostic Index risk. Immunohistochemical biomarkers for cell of origin and proliferation were performed.
  
  
  RESULTS
  With a median follow up of 62 months, time to progression and overall survival were 81% and 84%, respectively, and time to progression was 87%, 92% and 54% for low/low-intermediate, high-intermediate and high International Prognostic Index risk groups, respectively, at 5-years and beyond. The time to progression and event-free survival of germinal center B-cell lymphoma were 100% and 94%, respectively, and non-germinal center B-cell GCB diffuse large B-cell lymphoma were 67% and 58%, respectively, at 62 months (germinal center vs. non-germinal center B cell P=0.008). DA-EPOCH-R was tolerated without significant grade 4 non-hematologic toxicities.
  
  
  CONCLUSIONS
  These results provide the first confirmation by a multi-institutional group that DA-EPOCH-R provides high durable remissions in diffuse large B-cell lymphoma and is effective in both germinal center and non-germinal center B-cell subtypes. The trial was registered at ClinicalTrials.Gov (NCT00032019).
authors: Metabolism Branch, National Cancer Institute, Bethesda, MD 20892, USA. wilsonw@mail.nih.gov
authors: Wyndham H
authors: WH
authors: Wilson
authors: Sin-Ho
authors: SH
authors: Jung
authors: Pierluigi
authors: P
authors: Porcu
authors: David
authors: D
authors: Hurd
authors: Jeffrey
authors: J
authors: Johnson
authors: S Eric
authors: SE
authors: Martin
authors: Myron
authors: M
authors: Czuczman
authors: Raymond
authors: R
authors: Lai
authors: Jonathan
authors: J
authors: Said
authors: Amy
authors: A
authors: Chadburn
authors: Dan
authors: D
authors: Jones
authors: Kieron
authors: K
authors: Dunleavy
authors: George
authors: G
authors: Canellos
authors: Andrew D
authors: AD
authors: Zelenetz
authors: Bruce D
authors: BD
authors: Cheson
authors: Eric D
authors: ED
authors: Hsi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008479:Mediastinal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D012074:Remission Induction; D000069283:Rituximab; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D000069283:Rituximab; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone