Phase III randomised study of dexamethasone with or without oblimersen sodium for patients with advanced multiple myeloma.
Upregulation of the Bcl-2 antiapoptotic protein is reported to be associated with aggressive clinical course in multiple myeloma. Oblimersen sodium is a bcl-2 antisense oligonucleotide complementary to the first six codons of the open-reading frame of bcl-2 mRNA that can decrease transcription of Bcl-2 protein and increase myeloma cell susceptibility to cytotoxic agents. In this phase III randomised trial, we investigated in patients with relapsed/refractory myeloma whether addition of oblimersen to dexamethasone improved clinical outcomes vs. dexamethasone alone. Two hundred and twenty-four patients were randomised to receive either oblimersen/dexamethasone (N = 110) or dexamethasone alone (N = 114). The primary endpoint was time to tumor progression (TTP). Final results of this study demonstrated no significant differences between the two groups in TTP or objective response rate. The oblimersen/dexamethasone regimen was generally well tolerated with fatigue, fever and nausea, the most common adverse events reported.
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. asher.chanan-khan@roswellpark.org
Asher A
AA
Chanan-Khan
Ruben
R
Niesvizky
Raymond J
RJ
Hohl
Todd M
TM
Zimmerman
Neal P
NP
Christiansen
Gary J
GJ
Schiller
Natalie
N
Callander
John
J
Lister
Martin
M
Oken
Sundar
S
Jagannath
D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009325:Nausea / Q000139:chemically induced; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage; D013873:Thionucleotides / Q000008:administration & dosage; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D003907:Dexamethasone; C408162:oblimersen