title: Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma.
abstract: In multiple myeloma (MM), the addition of thalidomide or bortezomib to the standard oral melphalan/prednisone combination significantly increased response rate and event-free survival. In this multicenter phase 1/2 trial, dosing, safety, and efficacy of the 4-drug combination, bortezomib, melphalan, prednisone, and thalidomide (VMPT) was determined. Bortezomib was administered at 3 dose levels (1.0 mg/m2, 1.3 mg/m2, or 1.6 mg/m2) on days 1, 4, 15, and 22; melphalan was given at a dose of 6 mg/m2 on days 1 through 5 and prednisone at 60 mg/m2 on days 1 through 5. Thalidomide was delivered at 50 mg on days 1 through 35. Each course was repeated every 35 days. The maximum tolerated dose of bortezomib was 1.3 mg/m2. Thirty patients with relapsed or refractory MM were enrolled; 20 patients (67%) achieved a partial response (PR) including 13 patients (43%) who achieved at least a very good PR. Among 14 patients who received VMPT as second-line treatment, the PR rate was 79% and the immunofixation-negative complete response rate 36%. The 1-year progression-free survival was 61%, and the 1-year survival from study entry was 84%. Grade 3 nonhematologic adverse events included infections (5 patients), fatigue (1), vasculitis (1), and peripheral neuropathy (2); no grade 4 toxicities were recorded. Initial results showed that VMPT is an effective salvage therapy with a very high proportion of responses. The incidence of neurotoxicities was unexpectedly low.
authors.affiliation: Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliera (AO) S. Giovanni Battista, Turin, Italy. appalumbo@yahoo.com
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ambrosini
authors.forename: Giulia
authors.initials: G
authors.lastname: Benevolo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pregno
authors.forename: Norbert
authors.initials: N
authors.lastname: Pescosta
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Callea
authors.forename: Clotilde
authors.initials: C
authors.lastname: Cangialosi
authors.forename: Tommaso
authors.initials: T
authors.lastname: Caravita
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.forename: Sara
authors.initials: S
authors.lastname: Bringhen
authors.forename: Patrizia
authors.initials: P
authors.lastname: Falco
authors.forename: Ilaria
authors.initials: I
authors.lastname: Avonto
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D012449:Safety; D016879:Salvage Therapy; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone