title: Phase II trial of syncopated thalidomide, lenalidomide, and weekly dexamethasone in patients with newly diagnosed multiple myeloma.
abstract: Thalidomide and lenalidomide, in combination with dexamethasone, provide response rates ranging from 63%-79% after 4 cycles of therapy. Because of toxicities such as neuropathy and myelosuppression for thalidomide and lenalidomide, respectively, dose escalation has not been pursued. We evaluated a syncopated regimen of alternating weeks of thalidomide and lenalidomide to determine if a modified schedule allows for fewer dose reductions and, subsequently, superior efficacy. Although well tolerated, this phase II trial did not show superior efficacy compared with conventional dosing and scheduling of these agents.
  
  
  BACKGROUND
  Over the past decade, the novel agents thalidomide, lenalidomide, and bortezomib have emerged as effective treatment in patients with multiple myeloma (MM). Initially used in the relapse setting, these agents have been incorporated into frontline treatment algorithms. They have been combined in doublets with corticosteroids, in triplets with alkylators, or with each other. Because thalidomide and lenalidomide have different clinical activity and toxicity profiles, we designed a trial to evaluate a syncopated schedule of thalidomide and lenalidomide with weekly dexamethasone in patients with newly diagnosed MM to determine response and toxicity.
  
  
  METHODS
  Twenty-two patients with newly diagnosed MM were treated with syncopated thalidomide (200 mg on days 1-7 and 15-21), lenalidomide (25 mg on days 8-14 and 22-28 for the first cycle and 50 mg on the same schedule for subsequent cycles) with weekly dexamethasone (40 mg). Each cycle lasted 28 days. MM parameters were assessed at the end of each cycle. It was intended that the patients proceed to stem cell mobilization and autologous transplantation after 4 cycles of therapy.
  
  
  RESULTS
  The median number of cycles administered was 3.5. The overall response was 68%. The regimen was well tolerated by the majority of the patients; only patient discontinued treatment because of toxicity.
  
  
  CONCLUSIONS
  We conclude that a syncopated schedule of thalidomide and lenalidomide with weekly dexamethasone was tolerated well, with no unexpected toxicities. However the response rate, even using lenalidomide at 50 mg, was not superior to standard dosing of thalidomide or lenalidomide plus dexamethasone.
authors.affiliation: Myeloma Division, John Theurer Cancer Center at Hackensack UMC, Hackensack, NJ 07601, USA.
authors.forename: Madiha
authors.initials: M
authors.lastname: Tufail
authors.forename: David S
authors.initials: DS
authors.lastname: Siegel
authors.forename: Laura
authors.initials: L
authors.lastname: McBride
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bilotti
authors.forename: Erica
authors.initials: E
authors.lastname: Bello
authors.forename: Palka
authors.initials: P
authors.lastname: Anand
authors.forename: Karly
authors.initials: K
authors.lastname: Olivo
authors.forename: Urszula
authors.initials: U
authors.lastname: Bendarz
authors.forename: Ann
authors.initials: A
authors.lastname: McNeill
authors.forename: David H
authors.initials: DH
authors.lastname: Vesole
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D013792:Thalidomide / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide