Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma Journal Article


Authors: O'Connor, O. A.; Wright, J.; Moskowitz, C.; Muzzy, J.; Macgregor-Cortelli, B.; Stubblefield, M.; Straus, D.; Portlock, C.; Hamlin, P.; Choi, E.; Dumetrescu, O.; Esseltine, D.; Trehu, E.; Adams, J.; Schenkein, D.; Zelenetz, A. D.
Article Title: Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma
Abstract: Purpose: To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent and mantle-cell lymphoma (MCL). Patients and Methods: Patients with indolent and MCL were eligible. Bortezomib was given at a dose of 1.5 mg/m 2 on days 1, 4, 8, and 11. Patients were required to have received no more than three prior chemotherapy regimens, with at least 1 month since the prior treatment, 3 months from prior rituximab, and 7 days from prior corticosteroids; absolute neutrophil count more than 1,500/μL (500/μL if documented bone marrow involvement); and platelet count more than 50,000/μL. Results: Twenty-six patients were registered, of whom 24 were assessable. Ten patients had follicular lymphoma, 11 had MCL, three had small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL), and two had marginal zone lymphoma. The overall response rate was 58%, with one complete remission (CR), one unconfirmed CR (CRu), and four partial remissions (PR) among patients with follicular non-Hodgkin's lymphoma (NHL). All responses were durable, lasting from 3 to 24+ months. One patient with MCL achieved a CRu, four achieved a PR, and four had stable disease. One patient with MCL maintained his remission for 19 months. Both patients with marginal zone lymphoma achieved PR lasting 8+ and 11+ months, respectively. Patients with SLL or CLL have yet to respond. Overall, the drug was well tolerated, with only one grade 4 toxicity (hyponatremia). The most common grade 3 toxicities were lymphopenia (n = 14) and thrombocytopenia (n = 7). Conclusion: These data suggest that bortezomib was well tolerated and has significant single-agent activity in patients with certain subtypes of NHL.
Keywords: adult; clinical article; controlled study; aged; clinical trial; constipation; diarrhea; drug dose reduction; hypophosphatemia; side effect; rituximab; anorexia; bortezomib; proteasome inhibitor; controlled clinical trial; infection; mantle cell lymphoma; multiple cycle treatment; neutrophil count; phase 2 clinical trial; sensory neuropathy; nausea; thrombocytopenia; antineoplastic activity; hyperglycemia; hypomagnesemia; lymphocytopenia; hyperkalemia; hypoalbuminemia; hypokalemia; hyponatremia; prothrombin time; cancer regression; nonhodgkin lymphoma; neutrophil; drug response; lymphoma; thrombocyte count; cancer fatigue; phase 1 clinical trial; corticosteroid; chronic lymphatic leukemia; neuropathic pain; drug tolerance; follicular lymphoma; leukocyte; lymphocytoma; hypernatremia; partial thromboplastin time; hypocalcemia; vasculitis
Journal Title: Journal of Clinical Oncology
Volume: 23
Issue: 4
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2005-02-01
Start Page: 676
End Page: 684
Language: English
DOI: 10.1200/jco.2005.02.050
PROVIDER: scopus
PUBMED: 15613699
DOI/URL:
Notes: --- - "Cited By (since 1996): 340" - "Export Date: 24 October 2012" - "CODEN: JCOND" - "Source: Scopus"
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