title: Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study.
abstract: OBJECTIVE
  The aims of this multicenter study were to evaluate the response rate, progression-free survival, and toxicity of the combination of bortezomib, bendamustine, and rituximab in patients with follicular lymphoma whose disease was relapsed or refractory to prior treatment.
  
  
  METHODS
  Patients received five 35-day cycles of bortezomib, bendamustine, and rituximab: bortezomib administered intravenously (IV) at a dose of 1.6 mg/m(2) on days 1, 8, 15, and 22, cycles one to five; bendamustine 50, 70, or 90 mg/m(2) IV over a 60-minute infusion on days 1 and 2, cycles one to five; and rituximab 375 mg/m(2) on days 1, 8, 15, and 22 of cycle one and day 1 of subsequent cycles. Patients were assessed using the International Workshop Response Criteria, with the primary end point of 60% complete response rate.
  
  
  RESULTS
  Seventy-three patients were enrolled. During the dose-escalation phase, the maximum-tolerated dose for bendamustine was not reached; the 90 mg/m(2) dose level was expanded for the efficacy assessment, and a total of 63 patients received bendamustine 90 mg/m(2). In these 63 patients, the overall response rate was 88% (including 53% complete response). Median duration of response was 11.7 months (95% CI, 9.2 to 13.3). Median progression-free survival was 14.9 months (95% CI, 11.1 to 23.7). Toxicities were manageable; myelosuppression was the main toxicity (25% and 14% of patients experienced grade 3 to 4 neutropenia and grade 3 to 4 thrombocytopenia, respectively). Transient grade 3 to 4 neuropathy occurred in 11% of patients.
  
  
  CONCLUSIONS
  The combination of bortezomib, bendamustine, and rituximab is highly active in patients with follicular lymphoma who have received previous treatment.
authors.affiliation: MD Anderson Cancer Center, 1515 Holcombe Blvd #429, Houston, TX 77030-4009, USA. nfowler@mdanderson.org
authors.forename: Nathan
authors.initials: N
authors.lastname: Fowler
authors.forename: Brad S
authors.initials: BS
authors.lastname: Kahl
authors.forename: Peter
authors.initials: P
authors.lastname: Lee
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Matous
authors.forename: Amanda F
authors.initials: AF
authors.lastname: Cashen
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Jacobs
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Letzer
authors.forename: Bipinkumar
authors.initials: B
authors.lastname: Amin
authors.forename: Michael E
authors.initials: ME
authors.lastname: Williams
authors.forename: Sonali
authors.initials: S
authors.lastname: Smith
authors.forename: Alfred
authors.initials: A
authors.lastname: Saleh
authors.forename: Peter
authors.initials: P
authors.lastname: Rosen
authors.forename: Hongliang
authors.initials: H
authors.lastname: Shi
authors.forename: Sudha
authors.initials: S
authors.lastname: Parasuraman
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Cheson
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*; D000069461:Bendamustine Hydrochloride; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage; D011719:Pyrazines / Q000008:administration & dosage; D000069283:Rituximab; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001897:Boronic Acids; D009588:Nitrogen Mustard Compounds; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib; D000069461:Bendamustine Hydrochloride