A Phase 2 Study of Bortezomib in Relapsed, Refractory Myeloma

• Published in: The New England journal of medicine Vol. 348; no. 26; pp. 2609 - 2617
• Main Authors: Richardson, Paul G, Barlogie, Bart, Berenson, James, Singhal, Seema, Jagannath, Sundar, Irwin, David, Rajkumar, S. Vincent, Srkalovic, Gordan, Alsina, Melissa, Alexanian, Raymond, Siegel, David, Orlowski, Robert Z, Kuter, David, Limentani, Steven A, Lee, Stephanie, Hideshima, Teru, Esseltine, Dixie-Lee, Kauffman, Michael, Adams, Julian, Schenkein, David P, Anderson, Kenneth C
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 26.06.2003
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Apoptosis; Biological and medical sciences; Bone marrow; Boronic Acids - adverse effects; Boronic Acids - therapeutic use; Bortezomib; Chemotherapy; Cysteine Endopeptidases; Cytokines; Dexamethasone - therapeutic use; Dose-Response Relationship, Drug; Drug resistance; Drug Therapy, Combination; Female; General aspects; Hemoglobins - analysis; Humans; Male; Medical sciences; Middle Aged; Multienzyme Complexes - antagonists & inhibitors; Multiple Myeloma - drug therapy; Peripheral Nervous System Diseases - chemically induced; Pharmacology. Drug treatments; Prognosis; Protease Inhibitors - adverse effects; Protease Inhibitors - therapeutic use; Proteasome Endopeptidase Complex; Proteins; Pyrazines - adverse effects; Pyrazines - therapeutic use; Recurrence; Antineoplastic agent; Human; Immunopathology; Multicatalytic endopeptidase complex; Relapse; Enzyme; Treatment efficiency; Multicenter study; Malignant hemopathy; Myeloma; Refractory; Peptidases; Immunoglobulinopathy; Lymphoproliferative syndrome; Phase II trial; Secondary effect; Hydrolases
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa030288

Bortezomib, a member of a novel class of boronic acid dipeptides with the ability to inhibit the proteasome, was tested in patients with multiple myeloma whose condition was refractory to conventional chemotherapy. The drug induced responses in 35 percent of patients and was relatively nontoxic. Encouraging results with a new drug. Multiple myeloma accounts for approximately 14,600 new cases of cancer and 10,800 deaths annually in the United States. 1 Although conventional chemotherapy and high-dose therapy 2 with hematopoietic stem-cell rescue can prolong survival, few, if any, patients are cured. Salvage therapies for relapsed disease are equally disappointing, 3 , 4 and although thalidomide has shown promise, 5 , 6 new treatments are urgently needed. We report here the effects of bortezomib (Velcade [Millenium Pharmaceuticals], formerly known as PS-341), a selective inhibitor of the proteasome, in patients with multiple myeloma. The proteasome is a multi-enzyme complex that is present in all cells. It degrades proteins that regulate . . .