title: Thalidomide and CC-5013 in multiple myeloma: the University of Arkansas experience.
abstract: Based on the activity of single-agent thalidomide in relapsed/refractory multiple myeloma in a landmark phase II study of 169 patients conducted at the University of Arkansas for Medical Sciences (UAMS), UAMS initiated several trials of thalidomide and the more potent thalidomide analog CC-5013. In an ongoing trial evaluating thalidomide plus the proteasome inhibitor bortezomib and dexamethasone in patients with relapsed/refractory disease following stem cell transplantation, approximately 50% of patients have experienced a paraprotein reduction of 50% or greater. In patients without cytogenetic abnormalities, the estimated 12-month event-free and overall survival rates are 69% and 100%, respectively. In a second ongoing trial building on the UAMS Total Therapy I regimen, newly diagnosed patients are randomized to thalidomide or no thalidomide pretransplantation followed by consolidation therapy with dexamethasone and multiagent chemotherapy post-transplantation (Total Therapy II). Although the Total Therapy II regimen appears to be superior to the original Total Therapy I regimen, assessment of the effect of thalidomide on Total Therapy II is pending accrual completion. Lastly, based on the increased potency and reduced toxicity profile of CC-5013 compared with thalidomide, a study of CC-5013 in patients with relapsed/refractory disease following transplantation was initiated. Patients are randomized to CC-5013 25 mg daily for 20 days versus CC-5013 50 mg every other day for 10 days. Preliminary results indicate the superiority of the 25-mg arm, with 40% of patients randomized to that arm experiencing a paraprotein reduction of 50% or greater. These preliminary results corroborate the role for thalidomide and CC-5013 in relapsed/refractory and newly diagnosed multiple myeloma based on the UAMS phase II study as well as several other studies of these agents outside of UAMS.
authors.affiliation: University of Arkansas for Medical Sciences, 4301 W Markham, Slot 623, Little Rock, AR 72205, USA.
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001131:Arkansas; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D011480:Protease Inhibitors / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D016879:Salvage Therapy; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome; D014495:Universities
chemical_list: D000276:Adjuvants, Immunologic; D020533:Angiogenesis Inhibitors; D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D000077269:Lenalidomide