Low-dose vs. high-dose thalidomide for advanced multiple myeloma: a prospective trial from the Intergroupe Francophone du Myélome.
This multicentre prospective randomised trial compared the efficacy and safety of two doses of thalidomide in patients with relapsed or refractory myeloma. The study was designed to test the non-inferior efficacy and to confirm the better tolerability of low-dose thalidomide as compared to a higher dose. Four hundred patients were randomly assigned to receive either 100 or 400 mg/day of thalidomide. Dexamethasone treatment was added in both arms for patients with stable disease or treatment failure at 12 weeks. The primary endpoint was 1-year overall survival (OS). Thalidomide 100 mg/day was better tolerated than 400 mg/day with less high-grade somnolence, constipation, nausea/vomiting and peripheral neuropathy (P < 0.001, P = 0.007, P = 0.03 and P = 0.007, respectively). In the per-protocol population (PP), the estimated 1-year OS rates were of 74.5% (n = 149) and 67.3% (n = 156) in the 400 and 100 groups, respectively. The upper limit of the difference between these rates was of 15.6% higher than the non-inferiority acceptable limit of 12.75%, and the hypothesis of non-inferiority of 100 could not be established (P = 0.14). On the other hand, when intent-to-treat (ITT) population was analysed, the non-inferiority was demonstrated because the 1-year OS rates were of 72.8% (n = 195) and 68.8% (n = 205) in the same groups, leading to an upper limit of the difference of 11.49% lower than the non-inferiority acceptable limit. In addition, in patients alive 12 weeks postrandomisation and those who received thalidomide plus dexamethasone, there were no significant differences in response rates, time to progression, progression-free survival and OS between the two groups. Collectively, low-dose thalidomide 100 mg/day has significant activity in advanced myeloma with an improved safety profile and can be a good salvage therapy in combination with dexamethasone.
Service des Maladies du Sang, CHU, Lille, France. i-yakoub-agha@chru-lille.fr
Ibrahim
I
Yakoub-Agha
Jean-Yves
JY
Mary
Cyrille
C
Hulin
Chantal
C
Doyen
Gérald
G
Marit
Lotfi
L
Benboubker
Laurent
L
Voillat
Philippe
P
Moreau
Christian
C
Berthou
Anne-Marie
AM
Stoppa
Frédéric
F
Maloisel
Philippe
P
Rodon
Mamoun
M
Dib
Brigitte
B
Pegourie
Philippe
P
Casassus
Borhane
B
Slama
Ghandi
G
Damaj
Robert
R
Zerbib
Jean-Luc
JL
Harousseau
Mohamad
M
Mohty
Thierry
T
Facon
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D012307:Risk Factors; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D013792:Thalidomide