Current status of bortezomib in the treatment of multiple myeloma.
Bortezomib (formerly PS-341) has been the first proteasome inhibitor to enter clinical trials in cancer patients. Preclinical studies showing that this novel agent directly inhibits the proliferation of myeloma cells, induces their apoptosis, and abrogates paracrine tumor growth through alteration of interactions of myeloma and stromal cells and through nuclear factor kappaB-dependent cytokine secretion prompted the design of large phase II and III studies of bortezomib in patients with advanced relapsed and/or refractory multiple myeloma. Favorable results of these studies led to accelerated approval for use of bortezomib in patients with multiple myeloma who have progressed after at least their second therapy and, more recently, to expanded approval for second-line use in patients in whom one prior therapy has failed. Combination studies of bortezomib with various agents, including dexamethasone, DNA-damaging drugs (such as melphalan, cyclophosphamide, and doxorubicin), thalidomide, and lenalidomide, are currently ongoing in patients with both relapsed/refractory and newly diagnosed disease. Bortezomib may be the "backbone" for the development of more effective treatment strategies to improve patient outcome in multiple myeloma.
Cavo
Michele
M
Institute of Hematology and Medical Oncology "Seràgnoli", University of Bologna, via Massarenti 9, 40138, Bologna, Italy. mcavo@med.unibo.it
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000069286:Bortezomib; D045744:Cell Line, Tumor / Q000187:drug effects; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003131:Combined Modality Therapy; D016207:Cytokines / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000209:etiology; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016879:Salvage Therapy; D033581:Stem Cell Transplantation; D017154:Stromal Cells / Q000473:pathology; D014182:Transplantation, Autologous
D000970:Antineoplastic Agents; D001897:Boronic Acids; D016207:Cytokines; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib