title: A phase I/II study of bortezomib plus CHOP every 2 weeks (CHOP-14) in patients with advanced-stage diffuse large B-cell lymphomas.
abstract: BACKGROUND
  Bortezomib targets molecular dysregulation of nuclear factor-κB activation and cell cycle control, which are characteristic features of diffuse large B-cell lymphoma (DLBCL). We evaluated the safety and efficacy of bortezomib treatment with dose-dense cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) every 2 weeks (CHOP-14).
  
  
  METHODS
  Untreated DLBCL patients were enrolled. A phase I dose-escalation study with 1.0, 1.3, and 1.6 mg/m(2) bortezomib administration on day 1 and 4 in addition to the CHOP-14 regimen was performed to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT). Lenograstim 5 µg/kg/d was administered on day 4-13. The bortezomib dose from the phase I study was used in the phase II study.
  
  
  RESULTS
  Nine and 37 patients were enrolled in the phase I and phase II studies, respectively. The analysis of the phase II results (40 patients) included data of the 3 patients in the last MTD dose cohort of the phase I trial. During the phase I trial, no DLT was observed at any bortezomib dose; therefore, the recommended dose was 1.6 mg/m(2). In phase II, the overall response rate was 95% (complete response: 80%; partial response: 15%). Nine out of the 40 patients showed grade 3 sensory neuropathy, and 22 required at least 1 dose reduction. Three patients could not complete the intended 6 cycles of treatment because of severe neuropathy.
  
  
  CONCLUSIONS
  Bortezomib plus CHOP-14 was highly effective for the treatment of untreated DLBCL patients, but in many cases, dose or schedule modification was required to reduce neurotoxicity.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jeong Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Dok Hyun
authors.initials: DH
authors.lastname: Yoon
authors.forename: Geundoo
authors.initials: G
authors.lastname: Jang
authors.forename: Dae Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: Shin
authors.initials: S
authors.lastname: Kim
authors.forename: Chan-Sik
authors.initials: CS
authors.lastname: Park
authors.forename: Jooryung
authors.initials: J
authors.lastname: Huh
authors.forename: Won Seog
authors.initials: WS
authors.lastname: Kim
authors.forename: Jinny
authors.initials: J
authors.lastname: Park
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Soon Il
authors.initials: SI
authors.lastname: Lee
authors.forename: Cheolwon
authors.initials: C
authors.lastname: Suh