title: A randomized phase 2 trial of a preparative regimen of bortezomib, high-dose melphalan, arsenic trioxide, and ascorbic acid.
abstract: BACKGROUND
  Bortezomib is active for newly diagnosed and relapsed multiple myeloma, and it has synergistic activity with melphalan. The authors of this report conducted a randomized trial to determine the safety and efficacy of adding bortezomib to a preparative regimen of arsenic trioxide (ATO), ascorbic acid (AA), and melphalan.
  
  
  METHODS
  Among 60 patients who enrolled between October 2006 and September 2007, 58 patients underwent autologous transplantation with a preparative regimen of melphalan 200 mg/m(2) intravenously, AA 1000 mg daily intravenously for 7 days, and ATO 0.25 mg/kg intravenously for 7 days. Patients were randomized to receive no bortezomib (Group 1), bortezomib 1 mg/m(2) × 3 doses (Group 2), and bortezomib 1.5 mg/m(2) × 3 doses (Group 3). Primary endpoints were complete response (CR), grade IV toxicity, and 90-day treatment-related mortality (TRM). Secondary endpoints were progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  The median follow-up of all surviving patients was 36 months (range, 20-43 months). The CR rates in Groups 1, 2, and 3 were 20%, 10%, and 10%, respectively. Grade 3 and 4 nonhematologic toxicities and TRM were comparable. The median OS was not reached in the groups, whereas the median PFS in Groups 1, 2, and 3 was 17.8 months, 17.4 months, and 20.7 months, respectively. PFS and OS were significantly shorter in patients who had high-risk cytogenetics (P = .016 and P = .0001, respectively) and relapsed disease (P = .0001 and P = .0001, respectively) regardless of the treatment group.
  
  
  CONCLUSIONS
  Adding bortezomib to a preparative regimen of ATO, AA, and high-dose melphalan was safe and well tolerated in patients with multiple myeloma. There was no significant improvement in the CR rate, PFS, or OS in the bortezomib groups.
authors: Section of Bone Marrow Transplantation, Temple University, Philadelphia, Pennsylvania, USA.
authors: Manish
authors: M
authors: Sharma
authors: Hassan
authors: H
authors: Khan
authors: Peter F
authors: PF
authors: Thall
authors: Robert Z
authors: RZ
authors: Orlowski
authors: Roland L
authors: RL
authors: Bassett
authors: Nina
authors: N
authors: Shah
authors: Qaiser
authors: Q
authors: Bashir
authors: Simrit
authors: S
authors: Parmar
authors: Michael
authors: M
authors: Wang
authors: Jatin J
authors: JJ
authors: Shah
authors: Chitra M
authors: CM
authors: Hosing
authors: Uday R
authors: UR
authors: Popat
authors: Sergio A
authors: SA
authors: Giralt
authors: Richard E
authors: RE
authors: Champlin
authors: Muzaffar H
authors: MH
authors: Qazilbash
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000008:administration & dosage; D001804:Blood Transfusion, Autologous; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D010087:Oxides / Q000008:administration & dosage; D011379:Prognosis; D011719:Pyrazines / Q000008:administration & dosage*; D019172:Transplantation Conditioning
chemical_list: D001152:Arsenicals; D001897:Boronic Acids; D010087:Oxides; D011719:Pyrazines; D000069286:Bortezomib; D001205:Ascorbic Acid; D008558:Melphalan; D000077237:Arsenic Trioxide