A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma.
The phase 3 trial HOVON-50 was designed to evaluate the effect of thalidomide during induction treatment and as maintenance in patients with multiple myeloma who were transplant candidates. A total of 556 patients was randomly assigned to arm A: 3 cycles of vincristine, adriamycin, and dexamethasone, or to arm B: thalidomide 200 mg orally, days 1 to 28 plus adriamycin and dexamethasone. After induction therapy and stem cell mobilization, patients were to receive high-dose melphalan, 200 mg/m(2), followed by maintenance with alpha-interferon (arm A) or thalidomide 50 mg daily (arm B). Thalidomide significantly improved overall response rate as well as quality of the response before and after high dose melphalan. Best overall response rate on protocol was 88% and 79% (P = .005), at least very good partial remission 66% and 54% (P = .005), and complete remission 31% and 23% (P = .04), respectively, in favor of the thalidomide arm. Thalidomide also significantly improved event-free survival from median 22 months to 34 months (P < .001), and prolonged progression free from median 25 months to 34 months (P < .001). Median survival was longer in the thalidomide arm, 73 versus 60 months; however, this difference was not significant (P = .77). Patients randomized to thalidomide had strongly reduced survival after relapse. This trial was registered on www.controlled-trials.com as ISRCTN06413384.
Lokhorst
Henk M
HM
University Medical Center, Utrecht, The Netherlands. h.lokhorst@umcutrecht.nl
van der Holt
Bronno
B
Zweegman
Sonja
S
Vellenga
Edo
E
Croockewit
Sandra
S
van Oers
Marinus H
MH
von dem Borne
Peter
P
Wijermans
Pierre
P
Schaafsma
Ron
R
de Weerdt
Okke
O
Wittebol
Shulamiet
S
Delforge
Michel
M
Berenschot
Henriëtte
H
Bos
Gerard M
GM
Jie
Kon-Siong G
KS
Sinnige
Harm
H
van Marwijk-Kooy
Marinus
M
Joosten
Peter
P
Minnema
Monique C
MC
van Ammerlaan
Rianne
R
Sonneveld
Pieter
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
D013792:Thalidomide; D003907:Dexamethasone; D004317:Doxorubicin; D008558:Melphalan