title: Single agent bortezomib in the treatment of relapsed and refractory Hodgkin lymphoma: cancer and leukemia Group B protocol 50206.
abstract: Constitutive activation of nuclear factor-kappaB (NF-kappaB) has been described in patient-derived Reed - Sternberg cells and Hodgkin lymphoma (HL) cell lines and contributes to the proliferation and survival of HL. Therapeutic inhibition of the proteasome with bortezomib may inhibit over-expression of nuclear NF-kappaB by preventing degradation of IkappaB, which sequesters NF-kappaB in the cytoplasm. To evaluate this hypothesis, the Cancer and Leukemia Group B (CALGB) conducted a multi-institutional phase II trial of single agent bortezomib in patients with relapsed or refractory classical HL. Thirty patients received bortezomib 1.3 mg/m(2) on days 1, 4, 8, 11 and every 21 days for a median of 2 cycles (range, 1 - 8). Patients were heavily pre-treated with a median of four prior therapies, and 83% were previously transplanted. No responses were observed, 9 patients had stable disease, and 21 progressed. The median progression-free and overall survivals were 1.4 months [95% CI, (1.28, 1.91)] and 14.8 months [95% CI (11.2, 22.3)], respectively. Grade 3 - 4 adverse events, primarily thrombocytopenia, occurred in 15 patients. Therefore, although well tolerated, 1.3 mg/m(2) bortezomib administered biweekly has no single agent activity in relapsed/refractory classical HL.
authors.affiliation: Division of Hematology - Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA. kristie.blum@osumc.edu
authors.forename: Kristie A
authors.initials: KA
authors.lastname: Blum
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Donna
authors.initials: D
authors.lastname: Niedzwiecki
authors.forename: George P
authors.initials: GP
authors.lastname: Canellos
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Cheson
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Bartlett
mesh_terms: D000328:Adult; D001897:Boronic Acids / Q000008:administration & dosage* / Q000633:toxicity; D000069286:Bortezomib; D018450:Disease Progression; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage* / Q000633:toxicity; D016879:Salvage Therapy / Q000379:methods* / Q000401:mortality; D016019:Survival Analysis; D017211:Treatment Failure
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib