Perspectives for combination therapy to overcome drug-resistant multiple myeloma.
The introduction of melphalan and prednisone 40 years ago was a significant advance in the treatment of multiple myeloma (MM). In the following decades, significant advances were few, but included landmarks, such as the introduction of VAD and autologous transplantation during the 1980s and bisphosphonates in the 1990s. Although response rates to therapy were increased, overall survival was not significantly improved. In 1999, the treatment of myeloma was revolutionized by the introduction of thalidomide. Subsequently, the development of the immunomodulatory thalidomide analogues and the proteasome inhibitor bortezomib have impacted on response rates to therapy in relapsed and refractory myeloma and are currently being evaluated as primary therapy for myeloma. Early results suggest activity in combination with standard therapy to overcome drug resistance in patients with early stage disease and are changing treatment strategies in multiple myeloma. As an increasing number of other novel therapeutics is identified and mechanisms of resistance are elucidated, combinations of these drugs will be developed to optimize new therapeutic regimens.
Catley
Laurence
L
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Mayer 551, 44 Binney Street, Boston, MA 02115, USA. Laurence_Catley@dfci.harvard.edu
Tai
Yu-Tzu
YT
Chauhan
Dharminder
D
Anderson
Kenneth C
KC
D000077584:2-Methoxyestradiol; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics; D010087:Oxides / Q000008:administration & dosage; D061988:Proteasome Inhibitors; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013792:Thalidomide / Q000008:administration & dosage; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D001152:Arsenicals; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D010087:Oxides; D061988:Proteasome Inhibitors; D004958:Estradiol; D013792:Thalidomide; D000077584:2-Methoxyestradiol; D020794:Receptor Protein-Tyrosine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000077237:Arsenic Trioxide