title: VTD combination therapy with bortezomib-thalidomide-dexamethasone is highly effective in advanced and refractory multiple myeloma.
abstract: Bortezomib (V) was combined with thalidomide (T) and dexamethasone (D) in a phase I/II trial to determine dose-limiting toxicities (DLT's) and clinical activity of the VTD regimen in 85 patients with advanced and refractory myeloma. The starting dose of V was 1.0 mg/m(2) (days 1, 4, 8, 11, every 21 day) with T added from cycle 2 at 50 mg/day, with 50 mg increments per 10 patient cohorts, to a maximum dose of 200 mg. In the absence of DLT's, the same reiteration of T dose increases was applied with a higher dose of V=1.3 mg/m(2). D was added with cycle 4 in the absence of partial response (PR). Ninety-two percent had prior autotransplants, 74% had prior T and 76% abnormal cytogenetics. MTD was reached at V=1.3 mg/m(2) and T=150 mg. Minor response (MR) was recorded in 79%, and 63% achieved PR including 22% who qualified for near-complete remission. At 4 years, 6% remain event-free and 23% alive. Both OS and EFS were significantly longer in the absence of prior T exposure and when at least MR status was attained. The MMSET/FGFR3 molecular subtype was prognostically favorable, a finding since reported for a VTD-incorporating tandem transplant trial (Total Therapy 3) for untreated patients with myeloma (BJH 2008).
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: M
authors.initials: M
authors.lastname: Pineda-Roman
authors.forename: M
authors.initials: M
authors.lastname: Zangari
authors.forename: F
authors.initials: F
authors.lastname: van Rhee
authors.forename: E
authors.initials: E
authors.lastname: Anaissie
authors.forename: J
authors.initials: J
authors.lastname: Szymonifka
authors.forename: A
authors.initials: A
authors.lastname: Hoering
authors.forename: N
authors.initials: N
authors.lastname: Petty
authors.forename: J
authors.initials: J
authors.lastname: Crowley
authors.forename: J
authors.initials: J
authors.lastname: Shaughnessy
authors.forename: J
authors.initials: J
authors.lastname: Epstein
authors.forename: B
authors.initials: B
authors.lastname: Barlogie
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone