title: Bortezomib with or without irinotecan in relapsed or refractory colorectal cancer: results from a randomized phase II study.
abstract: OBJECTIVE
  To evaluate the efficacy and toxicity of bortezomib with or without irinotecan, in patients with relapsed or refractory colorectal cancer (CRC).
  
  
  METHODS
  Patients were randomly assigned in a 3:4 ratio to bortezomib 1.5 mg/m(2) (arm A) or bortezomib 1.3 mg/m(2) plus irinotecan 125 mg/m(2) (arm B). A treatment cycle of 21 days consisted of four bortezomib doses on days 1, 4, 8, and 11, plus, in arm B, irinotecan on days 1 and 8. The primary objective of this randomized, multicenter, open-label, phase II study was to determine tumor response to treatment. Secondary objectives were safety and tolerability.
  
  
  RESULTS
  A preplanned interim analysis to assess efficacy revealed inadequate activity, resulting in early termination of this study. A total of 102 patients were treated, 45 in arm A and 57 in arm B. Baseline characteristics were comparable. The investigator-assessed response rate was 0 in arm A and 3.5% in arm B (all partial responses). Adverse events in both treatment arms were as expected, with no significant additive toxicity. The most common grade >or= 3 adverse events reported, per patient, during the study were fatigue (27%), vomiting (13%), nausea (11%), and peripheral sensory neuropathy (11%) in arm A, and diarrhea (33%), fatigue (25%), neutropenia (23%), thrombocytopenia (18%), dyspnea (12%), abdominal pain (12%), dehydration (12%), and anemia (11%) in arm B.
  
  
  CONCLUSIONS
  Bortezomib alone or in combination with irinotecan was not effective in patients with relapsed or refractory CRC.
authors.affiliation: Continuum Cancer Centers of New York, St Luke's-Roosevelt Hospital, New York, NY, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Kozuch
authors.forename: Caio Max
authors.initials: CM
authors.lastname: Rocha-Lima
authors.forename: Tomislav
authors.initials: T
authors.lastname: Dragovich
authors.forename: Howard
authors.initials: H
authors.lastname: Hochster
authors.forename: Bert H
authors.initials: BH
authors.lastname: O'Neil
authors.forename: Omar T
authors.initials: OT
authors.lastname: Atiq
authors.forename: J Marc
authors.initials: JM
authors.lastname: Pipas
authors.forename: David P
authors.initials: DP
authors.lastname: Ryan
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D000077146:Irinotecan; D002166:Camptothecin