Multicenter Phase II Study of Bortezomib in Patients With Relapsed or Refractory Mantle Cell Lymphoma

Fisher, Richard I.; Bernstein, Steven H.; Kahl, Brad S.; Djulbegoviĉ, Benjamin; Robertson, Michael J.; Vos, Sven de; Epner, Elliot; Krishnan, Amrita; Leonard, John P.; Lonial, Sagar; Stadtmauer, Edward A.; O’Connor, Owen A.; Shi, Hongliang; Boral, Anthony; Goy, André

doi:10.1200/jco.2006.07.9665

Cited by 647 publications

(466 citation statements)

References 55 publications

(22 reference statements)

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“…Radioimmunotherapy might prove to be useful in patients with molecular, but probably not hematological, relapses. While the prospects for elderly are less bright, bortezomib, thalidomide and, presumably, lenalidomide containing combinations currently seem to be the best bet (4,5).…”

Section: MCLmentioning

confidence: 99%

E13 Non-Hodgkin lymphoma: how to proceed

Aurer

2007

Leukemia Research

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Section: MCLmentioning

confidence: 99%

E13 Non-Hodgkin lymphoma: how to proceed

Aurer

2007

Leukemia Research

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“…Approval of the dipeptide boronic acid proteasome inhibitor, bortezomib, for the treatment of relapsed multiple myeloma (MM; Richardson et al , 2005) and relapsed or refractory mantle cell lymphoma (Fisher et al , 2006) has spurred the development of other agents that target proteasome activity (Bennett & Kirk, 2008; Dick & Fleming, 2010; Kuhn et al , 2011). These agents vary from targeting individual active sites to targeting all three catalytic activities (Chauhan et al , 2005; Muchamuel et al , 2009).…”

mentioning

confidence: 99%

Clinical activity of carfilzomib correlates with inhibition of multiple proteasome subunits: application of a novel pharmacodynamic assay

et al. 2016

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SummaryWhile proteasome inhibition is a validated therapeutic approach for multiple myeloma (MM), inhibition of individual constitutive proteasome (c20S) and immunoproteasome (i20S) subunits has not been fully explored owing to a lack of effective tools. We utilized the novel proteasome constitutive/immunoproteasome subunit enzyme‐linked immunosorbent (ProCISE) assay to quantify proteasome subunit occupancy in samples from five phase I/II and II trials before and after treatment with the proteasome inhibitor carfilzomib. Following the first carfilzomib dose (15–56 mg/m2), dose‐dependent inhibition of c20S and i20S chymotrypsin‐like active sites was observed [whole blood: ≥67%; peripheral blood mononuclear cells (PBMCs): ≥75%]. A similar inhibition profile was observed in bone marrow–derived CD138+ tumour cells. Carfilzomib‐induced proteasome inhibition was durable, with minimal recovery in PBMCs after 24 h but near‐complete recovery between cycles. Importantly, the ProCISE assay can be used to quantify occupancy of individual c20S and i20S subunits. We observed a relationship between MM patient response (n = 29), carfilzomib dose and occupancy of multiple i20S subunits, where greater occupancy was associated with an increased likelihood of achieving a clinical response at higher doses. ProCISE represents a new tool for measuring proteasome inhibitor activity in clinical trials and relating drug action to patient outcomes.

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“…The proteasome inhibitor, bortezomib (also known as VEL-CADE or PS-341), represents a new class of anticancer drugs which has been shown to inhibit the growth and/or progression of human cancers, including multiple myeloma (Mitsiades et al, 2002;Rajkumar et al, 2005;Cavo, 2006;Fisher et al, 2006). Although it has been theoretically hypothesised that bortezomib abrogates the degradation of I-kB, which blocks the transcriptional activity of NF-kB, recent studies demonstrated that bortezomib elicits activation of multiple pathways in cancer cells, such as endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) pathways (Fribley et al, 2004;Nawrocki et al, 2005;Obeng et al, 2006;Pérez-Galán et al, 2006;Yang et al, 2006).…”

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Induction of heme oxygenase-1 by cobalt protoporphyrin enhances the antitumour effect of bortezomib in adult T-cell leukaemia cells

et al. 2007

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Adult T-cell leukaemia (ATL) is a lethal neoplasia derived from HTLV-1-infected T lymphocytes frequently exhibiting nuclear factorkB (NF-kB) activation. Despite the use of various treatment regimens, the prognosis of ATL is poor, and new treatment strategies are urgently needed. We therefore explored the effect and the molecular mechanism of a proteasome inhibitor, bortezomib, in ATL cells. We found bortezomib-induced cell death, and bortezomib suppressed constitutive NF-kB activation via I-kB stabilisation in three ATL cell lines (TaY, MT-2 and MT-4). An oligonucleotide DNA microarray analysis of TaY cells revealed upregulation of genes encoding heat shock proteins (HSPA1A, STIP1, HSPA1B, and HSPCA), genes related to protein folding (CDC37 and ANAPC5), Fasassociated factor 1(FAF1) and an oxidative stress-related gene, heme oxygenase-1(HMOX-1), known to be a target gene of hypoxiainducible gene-1 alpha (HIF-1 alpha). Cobalt protoporphyrin induced HMOX-1, instead of HIF-1 alpha expression and increased bortezomib-induced apoptosis in the presence of pharmacologically effective doses of bortezomib. In contrast, zinc protoporphyrin downregulated HMOX-1 expression, thereby partially inhibiting bortezomib-induced cell death. This indicates that HMOX-1 may modulate anticancer effects of bortezomib in ATL cells, and could be a molecular target in treating ATL patients.

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Multicenter Phase II Study of Bortezomib in Patients With Relapsed or Refractory Mantle Cell Lymphoma

Cited by 647 publications

References 55 publications

E13 Non-Hodgkin lymphoma: how to proceed

E13 Non-Hodgkin lymphoma: how to proceed

Clinical activity of carfilzomib correlates with inhibition of multiple proteasome subunits: application of a novel pharmacodynamic assay

Induction of heme oxygenase-1 by cobalt protoporphyrin enhances the antitumour effect of bortezomib in adult T-cell leukaemia cells

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