Multiple myeloma, frequently an indolent disease of the elderly, is fatal malignancy characterized by the accumulation of malignant plasma cells. The standard of care for multiple myeloma has remained relatively unchanged since the 1960's with the introduction of pulse melphalan and prednisone. Although high-dose chemotherapy and autologous stem cell support has significantly improved the response rates and overall survival for patients with multiple myeloma, this modality is not curative. As such, there is a pressing need to develop new, effective therapies for the treatment of this disease. Research over the past several decades has resulted in significant increases in the understanding of the biology of myeloma, including key molecular events, the importance of the marrow microenvironment and the potential role of immunotherapy. Paralleling this insight into the biology of myeloma, there has been an increase in the development of chemotherapeutic agents targeted for specific molecular events. As a result of this, there is the opportunity to test these new agents in multiple myeloma, targeting the key events in the pathogenesis of this disease. As such, the natural history of multiple myeloma can be altered by the rational application of new agents, selected because of the unique biologic and clinical features of this disease. To achieve this, the appropriate dose for new agents of potential therapeutic value in multiple myeloma will be determined through phase 1 studies, with a particular focus on special populations such as hematologic malignancies and patients with renal insufficiency. Furthermore, the activity of these agents that are selected based on its biology (drug resistance modifiers or target-based agents) or clinical features (indolent disease of the elderly) will be determined in multiple myeloma.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23CA087044-04
Application #
6945907
Study Section
Subcommittee G - Education (NCI)
Program Officer
Gorelic, Lester S
Project Start
2002-09-13
Project End
2007-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
4
Fiscal Year
2005
Total Cost
$131,058
Indirect Cost
Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Zimmerman, Todd M; Harlin, Helena; Odenike, Olatoyosi M et al. (2004) Dose-ranging pharmacodynamic study of tipifarnib (R115777) in patients with relapsed and refractory hematologic malignancies. J Clin Oncol 22:4816-22