title: Efficacy and toxicity of 2 schedules of frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone plus bortezomib in patients with B-cell lymphoma: a randomized phase 2 trial from the French Adult Lymphoma Study Group (GELA).
abstract: BACKGROUND
  Bortezomib demonstrated promising activity in lymphomas. The authors conducted a randomized phase 2 trial of frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with the addition of bortezomib in patients with B-cell lymphoma.
  
  
  METHODS
  Patients were randomized between 2 schedules of bortezomib, Arm A (Days 1, 4, 8, and 11) and Arm B (Days 1 and 8), combined with 6 cycles of R-CHOP. For the first patients (Step 1), bortezomib was given at a dose of 1 mg/m(2) in Arm A and 1.3 mg/m(2) in Arm B. For the next patients (Step 2), doses were increased to 1.3 mg/m(2) and 1.6 mg/m(2) in Arms A and B, respectively. The primary endpoint was the rate of complete response (CR) and unconfirmed CR (CR/CRu) after 6 cycles.
  
  
  RESULTS
  Forty-nine patients were included in the study, and 41 patients (84%) achieved a CR/CRu, ie, 18 of 20 patients (90%) in Arm A and 23 of 29 patients (79%) in Arm B. There were 6 partial responses and 2 patients with progressive disease. Neurologic toxicity occurred in 21 patients (43%) and was grade 2 in 11 patients (7 patients in Step 2) and grade 3 in 10 patients (9 patients in Step 2). Other grade 3 and 4 toxicities included constipation (n = 1), infections (n = 3), and cardiac events (n = 2). Grade 3 and 4 thrombocytopenia and leucopenia occurred in 14% and 41% of cycles, respectively.
  
  
  CONCLUSIONS
  R-CHOP + bortezomib was an effective regimen and produced an 84% CR rate. However, the dose-limiting neurotoxicity should be kept in mind for further trials with vinca alkaloids or other potentially neurotoxic drugs combination therapies.
authors: Hematology Department, Gustave Roussy Institute, Villejuif, France.
authors: Vincent
authors: V
authors: Ribrag
authors: Christian
authors: C
authors: Gisselbrecht
authors: Corinne
authors: C
authors: Haioun
authors: Gilles
authors: G
authors: Salles
authors: Jean-Baptiste
authors: JB
authors: Golfier
authors: Marjan
authors: M
authors: Ertault
authors: Christophe
authors: C
authors: Ferme
authors: Josette
authors: J
authors: Briere
authors: Pauline
authors: P
authors: Brice
authors: Nicolas
authors: N
authors: Mounier
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011719:Pyrazines / Q000008:administration & dosage*; D000069283:Rituximab; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D001897:Boronic Acids; D011719:Pyrazines; D000069283:Rituximab; D014750:Vincristine; D000069286:Bortezomib; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone