title: Rituximab with or without bevacizumab for the treatment of patients with relapsed follicular lymphoma.
abstract: BACKGROUND
  Inhibition of tumor angiogenesis by the interruption of VEGF pathway signaling is of therapeutic value in several solid tumors. Preclinical evidence supports similar importance of the pathway in non-Hodgkin lymphoma. In this randomized phase II trial, we compared the efficacy and toxicity of rituximab with bevacizumab versus single-agent rituximab, in patients with previously-treated follicular lymphoma.
  
  
  METHODS
  Patients (n = 60) were randomized (1:1) to receive rituximab (375 mg/m(2) intravenously [I.V.] weekly for 4 weeks) either as a single agent or with bevacizumab (10 mg/kg I.V. on days 3 and 15). Patients with an objective response or stable disease at week 12 received 4 additional doses of rituximab (at months 3, 5, 7, and 9); patients who received rituximab/bevacizumab also received bevacizumab 10 mg/kg I.V. every 2 weeks for 16 doses.
  
  
  RESULTS
  After a median follow-up of 34 months, PFS was improved in patients who received rituximab/bevacizumab compared with patients who received rituximab alone (median 20.7 vs. 10.4 months respectively; HR, 0.40 (95% confidence interval [CI], 0.20-0.80); P = .007). Overall survival was also improved numerically (73% vs. 53% at 4 years), but did not reach statistical significance (HR, 0.40 (95% CI, 0.15-1.05); P = .055). The addition of bevacizumab increased the toxicity of therapy, but both regimens were well tolerated (no grade 4 toxicity).
  
  
  CONCLUSIONS
  The addition of bevacizumab to rituximab significantly improved PFS. The role of angiogenesis inhibition in the treatment of follicular lymphoma requires further definition in larger clinical trials.
authors.affiliation: Sarah Cannon Research Institute (SCRI), Nashville, TN; Tennessee Oncology PLLC, Nashville, TN. Electronic address: John.Hainsworth@scresearch.net.
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.affiliation: Sarah Cannon Research Institute (SCRI), Nashville, TN; Tennessee Oncology PLLC, Nashville, TN.
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Greco
authors.affiliation: Tennessee Oncology PLLC, Nashville, TN.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Raefsky
authors.affiliation: Tennessee Oncology PLLC, Nashville, TN.
authors.forename: Dana S
authors.initials: DS
authors.lastname: Thompson
authors.affiliation: Florida Cancer Specialists, Ft Myers, FL.
authors.forename: Scott
authors.initials: S
authors.lastname: Lunin
authors.affiliation: Florida Cancer Specialists, Ft Myers, FL.
authors.forename: James
authors.initials: J
authors.lastname: Reeves
authors.affiliation: Sarah Cannon Research Institute (SCRI), Nashville, TN.
authors.forename: Lynn
authors.initials: L
authors.lastname: White
authors.affiliation: Sarah Cannon Research Institute (SCRI), Nashville, TN.
authors.forename: Raven
authors.initials: R
authors.lastname: Quinn
authors.affiliation: Sarah Cannon Research Institute (SCRI), Nashville, TN.
authors.forename: Laura M
authors.initials: LM
authors.lastname: DeBusk
authors.affiliation: Sarah Cannon Research Institute (SCRI), Nashville, TN; Tennessee Oncology PLLC, Nashville, TN.
authors.forename: Ian W
authors.initials: IW
authors.lastname: Flinn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012008:Recurrence; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000068258:Bevacizumab; D000069283:Rituximab
keywords: Angiogenesis; Anti-CD20; Lymphoma; VEGF; VEGF inhibitor