Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma.
OBJECTIVE
The long-term impact of thalidomide plus dexamethasone (thal/dex) as primary therapy for newly diagnosed multiple myeloma (MM) is unknown. The goal of this study was to compare thalidomide plus dexamethasone versus placebo plus dexamethasone (placebo/dex)as primary therapy for newly diagnosed MM.


METHODS
In this double-blind, placebo-controlled trial, patients with untreated symptomatic MM were randomized to thal/dex (arm A) or to placebo plus dexamethasone (dex) (arm B). Patients in arm A received oral thalidomide 50 mg daily, escalated to 100 mg on day 15, and to 200 mg from day 1 of cycle 2 (28-day cycles). Oral dex 40 mg was administered on days 1 through 4, 9 through 12, and 17 through 20 during cycles 1 through 4 and on days 1 through 4 only from cycle 5 onwards. Patients in arm B received placebo and dex, administered as in arm A. The primary end point of the study was time to progression. This study is registered at http://ClinicalTrials.gov (NCT00057564).


RESULTS
A total of 470 patients were enrolled (235 randomly assigned to thal/dex and 235 to placebo/dex). The overall response rate was significantly higher with thal/dex compared with placebo/dex (63% v 46%), P < .001. Time to progression (TTP) was significantly longer with thal/dex compared with placebo/dex (median, 22.6 v 6.5 months, P < .001). Grade 4 adverse events were more frequent with thal/dex than with placebo/dex (30.3% v 22.8%).


CONCLUSIONS
Thal/dex results in significantly higher response rates and significantly prolongs TTP compared with dexamethasone alone in patients with newly diagnosed MM.
Rajkumar
S Vincent
SV
Division of Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. rajkumar.vincent@mayo.edu
Rosiñol
Laura
L
Hussein
Mohamad
M
Catalano
John
J
Jedrzejczak
Wieslaw
W
Lucy
Lela
L
Olesnyckyj
Marta
M
Yu
Zhinuan
Z
Knight
Robert
R
Zeldis
Jerome B
JB
Bladé
Joan
J
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001315:Australia; D003907:Dexamethasone / Q000008:administration & dosage; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D013792:Thalidomide / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D013792:Thalidomide; D003907:Dexamethasone