title: Efficacy and safety of once-weekly bortezomib in multiple myeloma patients.
abstract: In a recent phase 3 trial, bortezomib-melphalan-prednisone-thalidomide followed by maintenance treatment with bortezomib-thalidomide demonstrated superior efficacy compared with bortezomib-melphalan-prednisone. To decrease neurologic toxicities, the protocol was amended and patients in both arms received once-weekly instead of the initial twice-weekly bortezomib infusions: 372 patients received once-weekly and 139 twice-weekly bortezomib. In this post-hoc analysis we assessed the impact of the schedule change on clinical outcomes and safety. Long-term outcomes appeared similar: 3-year progression-free survival rate was 50% in the once-weekly and 47% in the twice-weekly group (P > .999), and 3-year overall survival rate was 88% and 89%, respectively (P = .54). The complete response rate was 30% in the once-weekly and 35% in the twice-weekly group (P = .27). Nonhematologic grade 3/4 adverse events were reported in 35% of once-weekly patients and 51% of twice-weekly patients (P = .003). The incidence of grade 3/4 peripheral neuropathy was 8% in the once-weekly and 28% in the twice-weekly group (P < .001); 5% of patients in the once-weekly and 15% in the twice-weekly group discontinued therapy because of peripheral neuropathy (P < .001). This improvement in safety did not appear to affect efficacy. This study is registered at http://www.clinicaltrials.gov as NCT01063179.
authors.affiliation: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria S. Giovanni Battista, Torino, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Bringhen
authors.forename: Alessandra
authors.initials: A
authors.lastname: Larocca
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Maide
authors.initials: M
authors.lastname: Cavalli
authors.forename: Mariella
authors.initials: M
authors.lastname: Genuardi
authors.forename: Roberto
authors.initials: R
authors.lastname: Ria
authors.forename: Silvia
authors.initials: S
authors.lastname: Gentili
authors.forename: Francesca
authors.initials: F
authors.lastname: Patriarca
authors.forename: Chiara
authors.initials: C
authors.lastname: Nozzoli
authors.forename: Anna
authors.initials: A
authors.lastname: Levi
authors.forename: Tommasina
authors.initials: T
authors.lastname: Guglielmelli
authors.forename: Giulia
authors.initials: G
authors.lastname: Benevolo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Callea
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Rizzo
authors.forename: Clotilde
authors.initials: C
authors.lastname: Cangialosi
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.forename: Luca
authors.initials: L
authors.lastname: De Rosa
authors.forename: Anna Marina
authors.initials: AM
authors.lastname: Liberati
authors.forename: Mariella
authors.initials: M
authors.lastname: Grasso
authors.forename: Antonietta P
authors.initials: AP
authors.lastname: Falcone
authors.forename: Andrea
authors.initials: A
authors.lastname: Evangelista
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000453:epidemiology; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone