title: Phase I study of proteasome inhibitor bortezomib plus CHOP in patients with advanced, aggressive T-cell or NK/T-cell lymphoma.
abstract: The aim of the study was to determine the maximum tolerated dose (MTD) and safety of the combination of bortezomib and cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) as first-line therapy in advanced, aggressive T-cell lymphoma. Patients received increasing doses of bortezomib on days 1 and 8 (weekly schedule, 1.0, 1.3, and 1.6 mg/m(2)/dose) in addition to 750 mg/m(2) cyclophosphamide, 50 mg/m(2) doxorubicin, 1.4 mg/m(2) vincristine on day 1 and 100 mg/day prednisolone on days 1 to 5, every 3 weeks. Six cycles of therapy administered every 21 days were planned. Thirteen patients, who had stage III/IV chemonaive aggressive T-cell lymphoma, received a total of 55 cycles of treatment. One patient experienced hematologic dose-limiting toxicity (grade 4 neutropenia associated with febrile episode) at the 1.0 mg/m(2)/dose of bortezomib. There was no dose-limiting non-hematologic toxicity. The MTD was not reached at 1.6 mg/m(2) dose level of bortezomib. The overall complete remission rate in all patients was 61.5% (95% confidence interval = 31.6-86.1). Bortezomib can be safely combined with CHOP chemotherapy and constitutes an active regimen in advanced-stage, aggressive T-cell lymphoma patients. The recommended dose for subsequent phase II studies of bortezomib plus CHOP is 1.6 mg/m(2)/dose of bortezomib on days 1 and 8 every 3 weeks as first-line treatment.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Kangnam-Gu, Seoul, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Suh
authors.forename: H J
authors.initials: HJ
authors.lastname: Kang
authors.forename: B-Y
authors.initials: BY
authors.lastname: Ryoo
authors.forename: J
authors.initials: J
authors.lastname: Huh
authors.forename: Y H
authors.initials: YH
authors.lastname: Ko
authors.forename: H-S
authors.initials: HS
authors.lastname: Eom
authors.forename: K
authors.initials: K
authors.lastname: Kim
authors.forename: K
authors.initials: K
authors.lastname: Park
authors.forename: W S
authors.initials: WS
authors.lastname: Kim
mesh_terms: D000293:Adolescent; 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; D003520:Cyclophosphamide; D004317:Doxorubicin; D005260:Female; D006801:Humans; D016399:Lymphoma, T-Cell / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011241:Prednisone; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D014750:Vincristine
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D014750:Vincristine; D000069286:Bortezomib; D004317:Doxorubicin; D003520:Cyclophosphamide; D046988:Proteasome Endopeptidase Complex; D011241:Prednisone