Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma.
In this double-blind, placebo-controlled study, 363 patients with untreated multiple myeloma were randomized to receive either melphalan-prednisone and thalidomide (MPT) or melphalan-prednisone and placebo (MP). The dose of melphalan was 0.25 mg/kg and prednisone was 100 mg given daily for 4 days every 6 weeks until plateau phase. The dose of thalidomide/placebo was escalated to 400 mg daily until plateau phase and thereafter reduced to 200 mg daily until progression. A total of 357 patients were analyzed. Partial response was 34% and 33%, and very good partial response or better was 23% and 7% in the MPT and MP arms, respectively (P < .001). There was no significant difference in progression-free or overall survival, with median survival being 29 months in the MPT arm and 32 months in the MP arm. Most quality of life outcomes improved equally in both arms, apart from constipation, which was markedly increased in the MPT arm. Constipation, neuropathy, nonneuropathy neurologic toxicity, and skin reactions were significantly more frequent in the MPT arm. The number of thromboembolic events was equal in the 2 treatment arms. In conclusion, MPT had a significant antimyeloma effect, but this did not translate into improved survival. This trial was registered at www.clinicaltrials.gov as #NCT00218855.
Waage
Anders
A
Department of Hematology, St Olavs Hospital, Norwegian University of Science and Technology, Trondheim, Norway. anders.waage@ntnu.no
Gimsing
Peter
P
Fayers
Peter
P
Abildgaard
Niels
N
Ahlberg
Lucia
L
Björkstrand
Bo
B
Carlson
Kristina
K
Dahl
Inger Marie
IM
Forsberg
Karin
K
Gulbrandsen
Nina
N
Haukås
Einar
E
Hjertner
Oyvind
O
Hjorth
Martin
M
Karlsson
Torbjörn
T
Knudsen
Lene Meldgaard
LM
Nielsen
Johan Lanng
JL
Linder
Olle
O
Mellqvist
Ulf-Henrik
UH
Nesthus
Ingerid
I
Rolke
Jürgen
J
Strandberg
Maria
M
Sørbø
Jon Hjalmar
JH
Wisløff
Finn
F
Juliusson
Gunnar
G
Turesson
Ingemar
I
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D010919:Placebos; D011241:Prednisone / Q000008:administration & dosage; D012074:Remission Induction; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage; D016896:Treatment Outcome
D010919:Placebos; D013792:Thalidomide; D008558:Melphalan; D011241:Prednisone