title: Bortezomib, melphalan, and prednisone in elderly patients with relapsed/refractory multiple myeloma: a multicenter, open label phase 1/2 study.
abstract: BACKGROUND
  In elderly patients with newly diagnosed multiple myeloma (MM), the addition of bortezomib to standard, combined oral melphalan and prednisone (MP) significantly increases the response rate and event-free survival compared with MP alone.
  
  
  METHODS
  In this phase 1/2 trial, the authors assessed the dosing, efficacy, and safety of a lower dose-intensity MP schedule plus weekly bortezomib as salvage treatment for elderly patients with MM. To assess the maximum tolerated dose, 19 patients who had relapsed/refractory MM after 1 or 2 lines of treatment entered the first phase of the study. They received melphalan at a dose of 24 mg for 28 days; bortezomib 1.3 mg/m(2) on days 1, 8, 15, and 22; and prednisone at a dose of 50 mg every other day of a 28-day cycle for a total of 9 cycles. At the end of the first phase, based on the good efficacy and acceptable toxicity of this combination, an additional 23 patients were enrolled.
  
  
  RESULTS
  After a median follow-up of 21 months, of 42 patients who relapsed, 24 (57%) obtained at least a partial response, 4 had stable disease, and 11 had progressive disease. The median time to progression was 18 months, and the median overall survival was 30 months. Grade 3 and 4 toxicity was observed in 16 of 42 patients (38%) and was more frequent during the early cycles.
  
  
  CONCLUSIONS
  A weekly infusion of bortezomib associated with lower dose-intensity MP induced a high proportion of responses and was well tolerated in elderly patients with relapsed/refractory MM.
authors.affiliation: Hematology Service, Department of Cellular Biotechnology and Hematology, Sapienza University, Rome, Italy. petrucci@bce.uniroma1.it
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Petrucci
authors.forename: Anna
authors.initials: A
authors.lastname: Levi
authors.forename: Sara
authors.initials: S
authors.lastname: Bringhen
authors.forename: Simona
authors.initials: S
authors.lastname: Scotti
authors.forename: Fabiana
authors.initials: F
authors.lastname: Gentilini
authors.forename: Simone
authors.initials: S
authors.lastname: Russo
authors.forename: Agostina
authors.initials: A
authors.lastname: Siniscalchi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Larocca
authors.forename: Sara
authors.initials: S
authors.lastname: Grammatico
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008558:Melphalan / Q000008:administration & dosage; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D011241:Prednisone / Q000008:administration & dosage; D011719:Pyrazines / Q000008:administration & dosage; D012008:Recurrence
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone