title: Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma: a randomized study.
abstract: OBJECTIVE
  Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment, but no randomized trials have been published comparing these two treatment alternatives.
  
  
  METHODS
  Thalidomide- and bortezomib-naïve patients with melphalan refractory myeloma were randomly assigned to low-dose thalidomide + dexamethasone (Thal-Dex) or bortezomib + dexamethasone (Bort-Dex). At progression on either therapy, the patients were offered crossover to the alternative drug combination. An estimated 300 patients would be needed for the trial to detect a 50% difference in median PFS between the treatment arms.
  
  
  RESULTS
  After inclusion of 131 patients, the trial was prematurely closed because of low accrual. Sixty-seven patients were randomized to Thal-Dex and 64 to Bort-Dex. Progression-free survival was similar (median, 9.0 months for Thal-Dex and 7.2 for Bort-Dex). Response rate was similar (55% for Thal-Dex and 63% for Bort-Dex), but time to response was shorter (P < 0.05) and the VGPR rate higher (P < 0.01) for Bort-Dex. Time-to-other treatment after crossover was similar (median, 13.2 months for Thal-Dex and 11.2 months for Bort-Dex), as was overall survival (22.8 months for Thal-Dex and 19.0 for Bort-Dex). Venous thromboembolism was seen in seven patients and cerebrovascular events in four patients in the Thal-Dex group. Severe neuropathy, reactivation of herpes virus infections, and mental depression were more frequently observed in the Bort-Dex group. In the quality-of-life analysis, no difference was noted for physical function, pain, and global quality of life. Fatigue and sleep disturbances were significantly more prevalent in the Bort-Dex group.
  
  
  CONCLUSIONS
  Thalidomide (50-100 mg daily) in combination with dexamethasone seems to have an efficacy comparable with that of bortezomib and dexamethasone in melphalan refractory myeloma. However, the statistical strength of the results in this study is limited by the low number of included patients.
authors.affiliation: Department of Medicine, Lidköping Hospital, Lidköping, Sweden. martin.hjorth@vgregion.se
authors.forename: Martin
authors.initials: M
authors.lastname: Hjorth
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Hjertner
authors.forename: Lene Meldgaard
authors.initials: LM
authors.lastname: Knudsen
authors.forename: Nina
authors.initials: N
authors.lastname: Gulbrandsen
authors.forename: Erik
authors.initials: E
authors.lastname: Holmberg
authors.forename: Per Trøllund
authors.initials: PT
authors.lastname: Pedersen
authors.forename: Niels Frost
authors.initials: NF
authors.lastname: Andersen
authors.forename: Björn
authors.initials: B
authors.lastname: Andréasson
authors.forename: Rolf
authors.initials: R
authors.lastname: Billström
authors.forename: Kristina
authors.initials: K
authors.lastname: Carlson
authors.forename: Margaretha S
authors.initials: MS
authors.lastname: Carlsson
authors.forename: Max
authors.initials: M
authors.lastname: Flogegård
authors.forename: Karin
authors.initials: K
authors.lastname: Forsberg
authors.forename: Peter
authors.initials: P
authors.lastname: Gimsing
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Karlsson
authors.forename: Olle
authors.initials: O
authors.lastname: Linder
authors.forename: Hareth
authors.initials: H
authors.lastname: Nahi
authors.forename: Annika
authors.initials: A
authors.lastname: Othzén
authors.forename: Agneta
authors.initials: A
authors.lastname: Swedin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D018592:Cross-Over Studies; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011719:Pyrazines / Q000008:administration & dosage; D011788:Quality of Life; D012008:Recurrence; D013792:Thalidomide / Q000008:administration & dosage
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D008558:Melphalan