title: Bortezomib, doxorubicin and intermediate-dose dexamethasone (iPAD) therapy for relapsed or refractory multiple myeloma: a multicenter phase 2 study.
abstract: We previously conducted a phase 1 study of bortezomib, doxorubicin and intermediate-dose dexamethasone (iPAD) therapy and determined the optimal dose of bortezomib to be 1.0 mg/m(2). We then conducted a multicenter phase 2 study in patients with relapsed or refractory myeloma. Bortezomib 1.0 mg/m(2) was administered intravenously on days 1, 4, 8 and 11, in combination with intravenous doxorubicin 9 mg/m(2) on days 1-4, and dexamethasone 20 mg orally on days 1-2, 4-5, 8-9 and 11-12 at a 3-week interval for six cycles. The primary endpoint of this study was the complete remission (CR) rate, and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicity. Twenty-seven patients, median age of 63, were enrolled. An overall response rate was 89 % with CR rate of 30 %. The median PFS time was 12.1 months, and the median OS time was not reached. One patient died of pneumonia. Although the incidence of hematological toxicities was high, these were transient and manageable. The most common non-hematological toxicity was sensory neuropathy; grade 3 toxicity was observed in six patients (22 %) and treatment was discontinued in four. We conclude that iPAD therapy is feasible, and shows efficacy by inducing high response rates and long response duration.
authors.affiliation: Division of Medical Oncology, Hematology and Infectious Diseases, Department of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. yasushi@fukuoka-u.ac.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takamatsu
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Sunami
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Muta
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Morimoto
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Masakazu
authors.initials: M
authors.lastname: Higuchi
authors.forename: Kimiharu
authors.initials: K
authors.lastname: Uozumi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hata
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
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; D018572:Disease-Free Survival; D004317:Doxorubicin / 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; D015996:Survival Rate
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D004317:Doxorubicin