title: Optimization of rituximab for the treatment of DLBCL (I): dose-dense rituximab in the DENSE-R-CHOP-14 trial of the DSHNHL.
abstract: BACKGROUND
  To improve outcome of elderly patients with diffuse large B-cell lymphoma, dose-dense rituximab was evaluated in the prospective DENSE-R-CHOP-14 trial.
  
  
  METHODS
  Rituximab (375 mg/m(2)) was given on days 0, 1, 4, 8, 15, 22, 29, 43, 57, 71, 85, and 99 together with six CHOP-14 cycles. Results were to be compared with patients who had received the same chemotherapy in combination with eight 2-week applications of rituximab in RICOVER-60.
  
  
  RESULTS
  One hundred twenty-four patients are assessable. Dose-dense rituximab resulted in considerably higher serum levels during the first 50 days of treatment, but rituximab exposure time was not prolonged. Grade 3 and 4 infections were exceptionally high in the first 20 patients without anti-infective prophylaxis, but decreased after introduction of prophylaxis with aciclovir and cotrimoxazole in the remaining 104 patients (from 13% to 6% per cycle and from 35% to 18% per patient; P = 0.007 and P = 0.125, respectively). Patients with international prognostic index = 3-5 had higher complete response/complete response unconfirmed rates (82% versus 68%; P = 0.033) than in the respective RICOVER-60 population, but this did not translate into better long-term outcome, even though male hazard was decreased (event-free survival: from 1.5 to 1.1; progression-free survival: from 1.7 to 1.1; overall survival: from 1.4 to 1.0).
  
  
  CONCLUSIONS
  Dose-dense rituximab achieved higher rituximab serum levels, but was not more effective than eight 2-week applications in the historical control population, even though minor improvements in poor-prognosis and male patients cannot be excluded. The increased, though manageable toxicity, precludes its use in routine practice. Our results strongly support anti-infective prophylaxis with aciclovir and cotrimoxazole for all patients receiving R-CHOP.
authors.affiliation: Klinik für Innere Medizin I, Universitätsklinikum des Saarlandes, Homburg.
authors.forename: N
authors.initials: N
authors.lastname: Murawski
authors.affiliation: Klinik für Innere Medizin I, Universitätsklinikum des Saarlandes, Homburg. Electronic address: michael.pfreundschuh@uks.eu.
authors.forename: M
authors.initials: M
authors.lastname: Pfreundschuh
authors.affiliation: IMISE, University Leipzig, Leipzig.
authors.forename: S
authors.initials: S
authors.lastname: Zeynalova
authors.affiliation: Klinik für Innere Medizin I, Universitätsklinikum des Saarlandes, Homburg.
authors.forename: V
authors.initials: V
authors.lastname: Poeschel
authors.affiliation: Internal Medicine III, Klinikum Chemnitz, Chemnitz.
authors.forename: M
authors.initials: M
authors.lastname: Hänel
authors.affiliation: Klinik für Innere Medizin I, Universitätsklinikum des Saarlandes, Homburg.
authors.forename: G
authors.initials: G
authors.lastname: Held
authors.affiliation: Department of Haematology, Oncology and Stem Cell Transplantation, Asklepios Klinik St Georg, Hamburg.
authors.forename: N
authors.initials: N
authors.lastname: Schmitz
authors.affiliation: Innere Medizin, Universitätsklinikum Ulm, Ulm.
authors.forename: A
authors.initials: A
authors.lastname: Viardot
authors.affiliation: Klinikum Großhadern, Munich.
authors.forename: C
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Universitätsklinik Köln, Cologne.
authors.forename: M
authors.initials: M
authors.lastname: Hallek
authors.affiliation: Universitätsklinik Heidelberg, Heidelberg.
authors.forename: M
authors.initials: M
authors.lastname: Witzens-Harig
authors.affiliation: Universitätsklinikum Göttingen, Göttingen, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Trümper
authors.affiliation: Klinik für Innere Medizin I, Universitätsklinikum des Saarlandes, Homburg.
authors.forename: T
authors.initials: T
authors.lastname: Rixecker
authors.affiliation: Klinik für Innere Medizin I, Universitätsklinikum des Saarlandes, Homburg.
authors.forename: C
authors.initials: C
authors.lastname: Zwick
mesh_terms: D000212:Acyclovir / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000890:Anti-Infective Agents / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use; D003140:Communicable Disease Control; D003141:Communicable Diseases / Q000188:drug therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies; D000069283:Rituximab; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D000890:Anti-Infective Agents; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D003520:Cyclophosphamide; D011241:Prednisone; D000212:Acyclovir
keywords: diffuse large B-cell lymphoma; dose-dense rituximab; elderly; rituximab toxicity