title: Salvage therapy with pegylated liposomal doxorubicin, bortezomib, cyclophosphamide, and dexamethasone in relapsed/refractory myeloma patients.
abstract: OBJECTIVE
  In vitro studies have shown synergistic anti-myeloma effects of bortezomib combined with alkylating agents or anthracycline. We tested safety and efficacy of the combination of bortezomib, doxorubicin cyclophosphamide, and dexamethasone (ABCD) in the treatment of relapsed/refractory myeloma.
  
  
  METHODS
  ABCD consisted of bortezomib given intravenous (IV) at dosage 1.3 mg/m(2) , dexamethasone 40 mg IV on days 1, 4, 8, and 15, pegylated liposomal doxorubicin (PLD) 20 mg IV on days 1 and 15, plus cyclophosphamide 100 mg/d per os for 15 d. Between January 2008 and February 2009, 24 patients received a median of four 28-d ABCD cycles (range 1-6). All patients had been already treated with a median of two previous lines of treatment (range 1-6): 38% were resistant to previous therapies and 62% were relapsed.
  
  
  RESULTS
  Clinical response was observed in 12 patients (50%), including 29% of very good partial remissions or better. Side effects included hematological toxicity (31% any grade), grades 3-4 thrombocytopenia (9%), grades 3-4 anemia (17%). Non-hematological toxicity affected 32% of administered cycles and included gastrointestinal disturbances (54%), peripheral neuropathy (8%), and infections (8%). After a median follow-up of 21.5 months (range 2-44 months), median of progression-free survival (PFS) was 8.7 months and median overall survival was 22.5 months. Achieving at least partial response within the second cycle was associated with a better PFS (19.5 months vs. 3.5 months), P = 0.03, HR 0.35 (CI 95% 0.13-0.90).
  
  
  CONCLUSIONS
  ABCD is safe and effective for relapsed/refractory MM subjects previously treated with novel agents.
authors.affiliation: Department of Clinical and Molecular Biomedicine, Section of Haematology, University of Catania, Catania, Italy; Division of Hematology, Azienda Policlinico-OVE, Catania, Italy; Fondazione Umberto Veronesi, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Romano
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiarenza
authors.forename: Concetta
authors.initials: C
authors.lastname: Conticello
authors.forename: Maide
authors.initials: M
authors.lastname: Cavalli
authors.forename: Calogero
authors.initials: C
authors.lastname: Vetro
authors.forename: Cosimo
authors.initials: C
authors.lastname: Di Raimondo
authors.forename: Rosario
authors.initials: R
authors.lastname: Cunsolo
authors.forename: Giuseppe Alberto
authors.initials: GA
authors.lastname: Palumbo
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D005767:Gastrointestinal Diseases / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000209:etiology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D016879:Salvage Therapy; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide
keywords: bortezomib; cyclophosphamide; liposomal pegylated doxorubicin; multiple myeloma; salvage therapy