title: PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma.
abstract: Bortezomib (formerly PS-341) has significant activity in patients with relapsed multiple myeloma (MM), its efficacy is increased with the addition of dexamethasone and it demonstrates synergy with doxorubicin, thus providing the rationale for combination therapy with bortezomib, doxorubicin and dexamethasone (PAD). Patients with untreated MM received four 21-d cycles of PAD, comprising bortezomib 1.3 mg/m(2) on days 1, 4, 8 and 11, along with dexamethasone 40 mg on days 1-4, 8-11 and 15-18 during cycle 1 and days 1-4 during cycles 2-4. During days 1-4, patients also received 0, 4.5 or 9 mg/m(2) of doxorubicin at dose levels 1, 2, and 3 respectively. Following peripheral blood stem cell (PBSC) collection, patients received high-dose melphalan (MEL200) with PBSC transplantation (PBSCT). After PAD induction alone, 20 of 21 patients (95%) achieved at least a partial response (PR), including complete response (CR) in five patients (24%). Twenty of 21 had PBSC mobilized, and 18 of 20 received MEL200/PBSCT. In an intention-to-treat analysis, response rates were: CR 43%, near CR 14%, very good PR 24%, PR 14% and stable disease 5%. PAD was effective, did not prejudice subsequent PBSC collection, and should be further evaluated in prospective randomized trials.
authors.affiliation: Department of Haematology, St. Bartholomew's Hospital, London, UK.
authors.forename: Heather E
authors.initials: HE
authors.lastname: Oakervee
authors.forename: Rakesh
authors.initials: R
authors.lastname: Popat
authors.forename: Nicola
authors.initials: N
authors.lastname: Curry
authors.forename: Pat
authors.initials: P
authors.lastname: Smith
authors.forename: Curly
authors.initials: C
authors.lastname: Morris
authors.forename: Mary
authors.initials: M
authors.lastname: Drake
authors.forename: Samir
authors.initials: S
authors.lastname: Agrawal
authors.forename: Jim
authors.initials: J
authors.lastname: Stec
authors.forename: David
authors.initials: D
authors.lastname: Schenkein
authors.forename: Dixie-Lee
authors.initials: DL
authors.lastname: Esseltine
authors.forename: Jamie D
authors.initials: JD
authors.lastname: Cavenagh
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin