title: Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity.
abstract: OBJECTIVE
  Rituximab has been reported to have little activity in small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL) and to be associated with significant infusion-related toxicity. This study sought to decrease the initial toxicity and optimize the pharmacokinetics with an alternative treatment schedule.
  
  
  METHODS
  Thirty three patients with SLL/CLL received dose 1 of rituximab (100 mg) over 4 hours. In cohort I (n = 3; 250 mg/m(2)) and cohort II (n = 7; 375 mg/m(2)) rituximab was administered on day 3 and thereafter three times weekly for 4 weeks using a standard administration schedule. Cohort III (n = 23; 375 mg/m(2)) administered rituximab similar to cohort II for the first two treatments and then over 1 hour thereafter.
  
  
  RESULTS
  A total of 33 CLL/SLL patients were enrolled; only one patient discontinued therapy because of infusion-related toxicity. Thirteen patients developed transient hypoxemia, hypotension, or dyspnea that were associated with significant changes in baseline interleukin-6, interleukin-8, tumor necrosis factor alpha, and interferon gamma compared with those not experiencing such reactions. Infusion-related toxicity occurred more commonly in older (median age 73 v 62 years; P =.02) patients with no other pretreatment clinical or laboratory features predicting occurrence of these events. The overall response rate was 45% (3% CR, 42% PR; 95% CI 28% to 64%). Median response duration for these 15 patients was 10 months (95% CI, 6.8-13.2; range, 3 to 17+).
  
  
  CONCLUSIONS
  Rituximab administered thrice weekly for 4 weeks demonstrates clinical efficacy and acceptable toxicity. Initial infusion-related events seem to be cytokine mediated and resolve by the third infusion making rapid administration possible. Future combination studies of rituximab with other therapies in CLL seem warranted.
authors: Division of Hematology-Oncology, Department of Medicine and the Department of Clinical Investigation, Walter Reed Army Medical Center, Washington, DC, USA. byrd-2@medctr.osu.edu
authors: J C
authors: JC
authors: Byrd
authors: T
authors: T
authors: Murphy
authors: R S
authors: RS
authors: Howard
authors: M S
authors: MS
authors: Lucas
authors: A
authors: A
authors: Goodrich
authors: K
authors: K
authors: Park
authors: M
authors: M
authors: Pearson
authors: J K
authors: JK
authors: Waselenko
authors: G
authors: G
authors: Ling
authors: M R
authors: MR
authors: Grever
authors: A J
authors: AJ
authors: Grillo-Lopez
authors: J
authors: J
authors: Rosenberg
authors: L
authors: L
authors: Kunkel
authors: I W
authors: IW
authors: Flinn
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004417:Dyspnea / Q000139:chemically induced; D005260:Female; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D000860:Hypoxia / Q000139:chemically induced; D007262:Infusions, Intravenous; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D016207:Cytokines; D000069283:Rituximab