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 1.3 mg/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. Copyright © 2011 John Wiley & Sons A/S.

• MeSH
• adjuvantní radioterapie MeSH
• alkalická fosfatasa krev   MeSH
• biologické markery krev   MeSH
• bortezomib MeSH
• buněčná diferenciace MeSH
• kyseliny boronové aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melfalan aplikace a dávkování   MeSH
• mezibuněčné signální peptidy a proteiny krev   MeSH
• mnohočetný myelom patofyziologie   patologie   MeSH
• nemoci kostí etiologie   MeSH
• osteoblasty MeSH
• prednison aplikace a dávkování   MeSH
• protokoly antitumorózní kombinované chemoterapie * terapeutické užití   MeSH
• pyraziny aplikace a dávkování   MeSH
• remodelace kosti * účinky léků   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH

OBJECTIVES: This subanalysis of the phase 3 VISTA trial aimed to assess the frequency, characteristics and reversibility of, and prognostic factors for, bortezomib-associated peripheral neuropathy (PN) in newly diagnosed patients with multiple myeloma ineligible for high-dose therapy who received bortezomib plus melphalan-prednisone. METHODS: Patients received nine 6-wk cycles of VMP (bortezomib 1.3 mg/m(2), days 1, 4, 8, 11, 22, 25, 29, 32, cycles 1-4, and days 1, 8, 22, 29, cycles 5-9; melphalan 9 mg/m(2), days 1-4, cycles 1-9; and prednisone 60 mg/m(2), days 1-4, cycles 1-9). RESULTS: Overall, 47% of patients receiving VMP developed PN, including 19% grade 2 and 13% grade > 3 (<1% grade 4). The PN incidence was dose-related and reached a plateau at a cumulative bortezomib dose of approximately 45 mg/m(2). Median time to PN onset was 2.3 months. Bortezomib-associated PN was reversible; 79% of events improved by at least one NCI CTCAE grade within a median of 1.9 months and 60% completely resolved within a median of 5.7 months, with reversibility similar in responding and non-responding patients. By multivariate analysis, baseline neuropathy was the only consistent risk factor for any PN [hazard ratio (HR) 1.785, P=0.0065], grade > 2 PN (HR 2.205, P=0.0032), and grade > 3 PN (HR 2.438, P=0.023); age, pre-existing diabetes, International Staging System stage, obesity, and creatinine clearance did not affect the overall rate of PN. CONCLUSIONS: Rates of bortezomib-induced PN in the frontline setting were similar to those in relapsed patients and resolved in most cases. Copyright © 2010 John Wiley & Sons A/S.

• MeSH
• bortezomib MeSH
• kyseliny boronové * aplikace a dávkování   toxicita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melfalan aplikace a dávkování   škodlivé účinky   MeSH
• mnohočetný myelom * farmakoterapie   komplikace   MeSH
• multivariační analýza MeSH
• nemoci periferního nervového systému * etiologie   chemicky indukované   MeSH
• prednison aplikace a dávkování   škodlivé účinky   MeSH
• protokoly antitumorózní kombinované chemoterapie * MeSH
• pyraziny * toxicita   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH