title: A multicenter retrospective analysis of adverse events in Korean patients using bortezomib for multiple myeloma.
abstract: The proteasome inhibitor bortezomib has demonstrated clinical activity in patients with multiple myeloma (MM). Adverse events, including thrombocytopenia and peripheral neuropathy, have affected 30% to 60% of patients overall, and interrupted therapy in 10% to 20%. No prior toxicity data are available for Asian patients who have used bortezomib for MM. We used National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, to review the clinical records of patients with an MM diagnosis from 25 centers in Korea. The included patients were treated with bortezomib alone or in combination with other agents, including thalidomide. Ninety-five MM patients were treated. The patients had a median age of 60 years (range, 42-77 years). The median number of previous treatments was 3 (range, 0-10), and 39% of the patients had been treated with 4 or more major classes of agents, including thalidomide (67%), and autologous stem cell transplantation (51%). Regimens included bortezomib only in 38 patients (40%), bortezomib plus dexamethasone in 34 patients (36%), and bortezomib plus a thalidomide-containing regimen in 23 patients (24%). The analysis of patient response to therapy revealed a complete response (CR) or a near-CR in 31 patients (33%) and a partial response in 30 patients (32%), for an objective response rate of 65% in 93 patients. The most common adverse events reported were thrombocytopenia (47%), sensory neuropathy (42%), anemia (31%), and leukopenia (31%). Thirteen patients (14%) stopped therapy because of adverse events (neuropathy, 8; infection, 4; diarrhea, 1). Neuropathy greater than grade 2 was more frequent in patients who received 4 or more prior therapy regimens (17/37) than in those who received 3 or fewer (14/58). In addition, therapy including thalidomide was significantly correlated with neuropathy of grades 1 to 3 (P = .001). We identified 6 therapy-related deaths (6%) within 20 days after the last dose of bortezomib. The causes of death were infection in 3 patients, disease progression in 2 patients, and suicide in 1 patient. The incidences of thrombocytopenia and neurotoxicity were similar; however, gastrointestinal toxicities were relatively low in Korean patients compared with those reported in Western studies. Significant neuropathy was associated with the number of prior regimens and combination with thalidomide. These findings provide useful information for clinicians and patients using bortezomib.
authors.affiliation: Gachon Medical School, Incheon, Korea.
authors.forename: Soo-Mee
authors.initials: SM
authors.lastname: Bang
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Yoon
authors.forename: Seonyang
authors.initials: S
authors.lastname: Park
authors.forename: Chang-Ki
authors.initials: CK
authors.lastname: Min
authors.forename: Chun-Choo
authors.initials: CC
authors.lastname: Kim
authors.forename: Cheolwon
authors.initials: C
authors.lastname: Suh
authors.forename: Sang Kyun
authors.initials: SK
authors.lastname: Sohn
authors.forename: Yoo-Hong
authors.initials: YH
authors.lastname: Min
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
authors.forename: Kihyun
authors.initials: K
authors.lastname: Kim
authors.forename: Chu-Myong
authors.initials: CM
authors.lastname: Seong
authors.forename: Hwi-Joong
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Kyung Sam
authors.initials: KS
authors.lastname: Cho
authors.forename: Deog-Yeon
authors.initials: DY
authors.lastname: Jo
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Lee
authors.forename: Na-Ri
authors.initials: NR
authors.lastname: Lee
authors.forename: Chul Soo
authors.initials: CS
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D044466:Asian People; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects*; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000401:mortality; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects; D014182:Transplantation, Autologous
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone