title: VAD-doxil versus VAD-doxil plus thalidomide as initial treatment for multiple myeloma: results of a multicenter randomized trial of the Greek Myeloma Study Group.
abstract: BACKGROUND
  We have previously demonstrated that vincristine, liposomal doxorubicin and dexamethasone (VAD-doxil) is equally effective with VAD-bolus yielding objective response rates of 61% as first-line treatment in multiple myeloma (MM). In a phase II study, the addition of thalidomide to VAD-doxil (TVAD-doxil) proved feasible and increased response rate to 74%. The aim of the present multicenter prospective randomized clinical trial was to compare the efficacy and toxicity of VAD-doxil and TVAD-doxil in previously untreated MM patients.
  
  
  METHODS
  We enrolled 232 newly diagnosed MM patients aged <75 years, 115 randomized to VAD-doxil (arm A) and 117 to TVAD-doxil (arm B). Patients in arm A received vincristine 2 mg i.v. and liposomal doxorubicin 40 mg/m(2) i.v., on day 1 and dexamethasone 40 mg p.o. daily on days 1-4, 9-12 and 17-20 for the first cycle and on days 1-4 for the next three cycles. Patients in arm B received additionally thalidomide 200 mg p.o. daily, at bedtime. Treatment was administered every 28 days.
  
  
  RESULTS
  On an intention-to-treat basis, at least partial response was observed, in 62.6% and in 81.2% of patients randomized to arms A and B, respectively (P = 0.003). Progression-free survival (PFS) at 2 years was 44.8% in arm A and 58.9% in arm B (P = 0.013). Overall survival (OS) at 2 years was 64.6% and 77%, in arms A and B, respectively (P = 0.037). Considering overall toxicity, constipation, peripheral neuropathy, dizziness/somnolence, skin rash and edema were significantly higher in arm B compared with arm A (P < 0.01), but grade 3-4 toxicities were low and similar in both arms.
  
  
  CONCLUSIONS
  The addition of thalidomide to VAD-doxil increases response and PFS rates and probably OS in previously untreated myeloma patients. The superiority of efficacy counterbalances the higher overall toxicity of TVAD-doxil.
authors: Theagenion Cancer Center, Thessaloniki, Greece.
authors: K
authors: K
authors: Zervas
authors: D
authors: D
authors: Mihou
authors: E
authors: E
authors: Katodritou
authors: A
authors: A
authors: Pouli
authors: C H
authors: CH
authors: Mitsouli
authors: A
authors: A
authors: Anagnostopoulos
authors: S
authors: S
authors: Delibasi
authors: M C
authors: MC
authors: Kyrtsonis
authors: N
authors: N
authors: Anagnostopoulos
authors: E
authors: E
authors: Terpos
authors: P
authors: P
authors: Zikos
authors: A
authors: A
authors: Maniatis
authors: M A
authors: MA
authors: Dimopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D013792:Thalidomide; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin