Τίτλος:
Fewer bone disease events, improvement in bone remodeling, and evidence of bone healing with bortezomib plus melphalan-prednisone vs. Melphalan-prednisone in the phase III VISTA trial in multiple myeloma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objectives: Bone disease is a key presenting feature of myeloma. This post hoc analysis of the phase III VISTA trial of bortezomib plus melphalan-prednisone (VMP) vs. MP in previously untreated myeloma patients assessed clinical bone disease events and changes in alkaline phosphatase (ALP), a marker for osteoblast activation, and serum Dickkopf-1 (DKK-1), an inhibitor of osteoblast differentiation, during treatment. Methods: Patients received nine 6-wk cycles of VMP (bortezomib 1.3mg/m 2, days 1, 4, 8, 11, 22, 25, 29, 32, cycles 1-4, days 1, 8, 22, 29, cycles 5-9, plus melphalan 9mg/m 2 and prednisone 60mg/m 2, days 1-4, cycles 1-9; N=344) or MP alone (N=338). Results: Rates of bisphosphonates use during treatment (73% vs. 82%), progression because of worsening bone disease (3% vs. 11%), and requirement for subsequent radiotherapy (3% vs. 8%) were lower with VMP vs. MP. Median maximum ALP increase was significantly higher with VMP vs. MP overall (49.7% vs. 30.3%, P=0.029), and higher by response group (complete response [CR]: 68.7% vs. 43.9%; partial response [PR]: 41.5% vs. 31.2%). Greater maximum ALP increase was strongly associated with achievement of CR (P≤0.0001) and CR/PR (P≤0.01). Median DKK-1 decreased with VMP by 694.4pg/mL and increased with MP by 1273.3pg/mL from baseline to day 4 (P=0.0069). Available radiologic data revealed evidence of bone healing in 6/11 VMP-treated patients, who achieved best responses of three CR, one PR, and two stable disease. Conclusions: These results suggest a positive effect of bortezomib on bone metabolism and potentially bone healing in myeloma. © 2011 John Wiley and Sons A/S.
Συγγραφείς:
Delforge, M.
Terpos, E.
Richardson, P.G.
Shpilberg, O.
Khuageva, N.K.
Schlag, R.
Dimopoulos, M.A.
Kropff, M.
Spicka, I.
Petrucci, M.T.
Samoilova, O.S.
Mateos, M.-V.
Magen-Nativ, H.
Goldschmidt, H.
Esseltine, D.-L.
Ricci, D.S.
Liu, K.
Deraedt, W.
Cakana, A.
Van de Velde, H.
San Miguel, J.F.
Περιοδικό:
European Journal of Haematology
Λέξεις-κλειδιά:
alkaline phosphatase; bisphosphonic acid derivative; bortezomib; dickkopf 1 protein; melphalan; prednisone, adult; aged; alkaline phosphatase blood level; article; bone disease; bone metabolism; bone remodeling; cancer radiotherapy; computer assisted tomography; controlled study; drug effect; female; fracture healing; human; hypercalcemia; major clinical study; male; multiple cycle treatment; multiple myeloma; osteoblast; phase 3 clinical trial; priority journal; randomized controlled trial; skull radiography; treatment response, Aged; Aged, 80 and over; Alkaline Phosphatase; Antineoplastic Combined Chemotherapy Protocols; Biological Markers; Bone Diseases; Bone Remodeling; Boronic Acids; Cell Differentiation; Female; Humans; Intercellular Signaling Peptides and Proteins; Male; Melphalan; Middle Aged; Multiple Myeloma; Osteoblasts; Prednisone; Pyrazines; Radiotherapy, Adjuvant
DOI:
10.1111/j.1600-0609.2011.01599.x
