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Clinical Pharmacology

The Emerging Role of Targeted Therapy for Hematologic Malignancies: Update on Bortezomib and Tipifarnib

^aInstitut Gustave-Roussy, Villejuif, France; ^bNational Cancer Research Institute, London, United Kingdom; ^cMedical University of Vienna, Vienna, Austria; ^dUniversity Hospital Nantes, Nantes, France; ^eErasmus University Medical Center, Rotterdam, The Netherlands; ^fUniversity Hospital of Salamanca, Salamanca, Spain

Key Words. Bortezomib • Multiple myeloma • Proteasome inhibition • Tipifarnib • Targeted therapy

Correspondence: Jean-Pierre Armand, Institut Gustave-Roussy, Dept. of Medicine, 39 Rue Camille-Desmoulins, Villejuif Cedex 94805, France. Telephone: 33-5-61-42-4201; Fax: 33-5-61-59-2928; e-mail: armand.jean-pierre{at}claudiusregaud.fr

As therapy for hematologic malignancy evolves, new regimens and novel agents that target specific cellular processes allow a more optimistic prognosis for many patients. Bortezomib and tipifarnib are two new, targeted treatments for hematologic malignancies. Bortezomib, a proteasome inhibitor, has shown impressive efficacy in patients with relapsed multiple myeloma and as initial treatment, including before autologous stem cell transplantation. It has been studied as monotherapy and in combination with standard treatments such as dexamethasone, and with newer agents such as the immunomodulators thalidomide and lenalidomide; response is encouraging, even in patients who have relapsed after previously receiving components of a regimen as single agents. Bortezomib is generally well tolerated, including in combination with novel and conventional agents. Tipifarnib is a specific inhibitor of farnesyltransferase. Clinical trials in patients with high-risk acute leukemias and myelodysplastic syndromes have demonstrated good efficacy with tipifarnib. Continued investigation with these new, targeted treatments will further define their use as treatment options in patients with hematologic cancer.

Disclosure of potential conflicts of interest is found at the end of this article.

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