title: Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial.
abstract: BACKGROUND
  Since 1960, oral melphalan and prednisone (MP) has been regarded as the standard of care in elderly multiple myeloma patients. This multicentre randomised trial compared oral MP plus thalidomide (MPT) with MP alone in patients aged 60-85 years.
  
  
  METHODS
  Patients with newly diagnosed multiple myeloma were randomly assigned to receive oral MP for six 4-week cycles plus thalidomide (n=129; 100 mg per day continuously until any sign of relapse or progressive disease) or MP alone (n=126). Analysis was intention-to-treat. This study is registered at , number NCT00232934.
  
  
  RESULTS
  Patients treated with thalidomide had higher response rates and longer event-free survival (primary endpoints) than patients who were not. Combined complete or partial response rates were 76.0% for MPT and 47.6% for MP alone (absolute difference 28.3%, 95% CI 16.5-39.1), and the near-complete or complete response rates were 27.9% and 7.2%, respectively. 2-year event-free survival rates were 54% for MPT and 27% for MP (hazard ratio [HR] for MPT 0.51, 95% CI 0.35-0.75, p=0.0006). 3-year survival rates were 80% for MPT and 64% for MP (HR for MPT 0.68, 95% CI 0.38-1.22, p=0.19). Rates of grade 3 or 4 adverse events were 48% in MPT patients and 25% in MP patients (p=0.0002). Introduction of enoxaparin prophylaxis reduced rate of thromboembolism from 20% to 3% (p=0.005).
  
  
  CONCLUSIONS
  Oral MPT is an effective first-line treatment for elderly patients with multiple myeloma. Anticoagulant prophylaxis reduces frequency of thrombosis. Longer follow-up is needed to assess effect on overall survival.
authors.affiliation: Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliera S Giovanni Battista, 10126 Torino, Italy. appalumbo@yahoo.com
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.forename: Sara
authors.initials: S
authors.lastname: Bringhen
authors.forename: Tommaso
authors.initials: T
authors.lastname: Caravita
authors.forename: Emanuela
authors.initials: E
authors.lastname: Merla
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Capparella
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Callea
authors.forename: Clotilde
authors.initials: C
authors.lastname: Cangialosi
authors.forename: Mariella
authors.initials: M
authors.lastname: Grasso
authors.forename: Fausto
authors.initials: F
authors.lastname: Rossini
authors.forename: Monica
authors.initials: M
authors.lastname: Galli
authors.forename: Lucio
authors.initials: L
authors.lastname: Catalano
authors.forename: Elena
authors.initials: E
authors.lastname: Zamagni
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Petrucci
authors.forename: Valerio
authors.initials: V
authors.lastname: De Stefano
authors.forename: Manuela
authors.initials: M
authors.lastname: Ceccarelli
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ambrosini
authors.forename: Ilaria
authors.initials: I
authors.lastname: Avonto
authors.forename: Patrizia
authors.initials: P
authors.lastname: Falco
authors.forename: Giovannino
authors.initials: G
authors.lastname: Ciccone
authors.forename: Anna Marina
authors.initials: AM
authors.lastname: Liberati
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D011241:Prednisone / Q000008:administration & dosage; D013792:Thalidomide / Q000008:administration & dosage
chemical_list: D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D013792:Thalidomide; D008558:Melphalan; D011241:Prednisone