title: Hematologic malignancies: new developments and future treatments.
abstract: An increasing number of unique active new chemotherapeutic and biologic agents are currently available for clinical research studies. Nucleoside analogs in development for non-Hodgkin's lymphoma (NHL) include clofarabine, troxacitabine, and bendamustine, a hybrid of an alkylating nitrogen mustard group and a purine-like benzimidazole, with demonstrated activity in NHL. Drugs directed at the cell cycle include flavopiridol and UCN-01. The proteasome plays a pivotal role in cellular protein regulation and activation of NFkappaB, which maintains cell viability through the transcription of inhibitors of apoptosis. PS-341 is a specific, selective inhibitor of the 26S proteasome which induces apoptosis and has activity in cell types characterized by overexpression of Bcl-2. Response rates of 50%, including complete remissions, have been reported using this agent in patients with refractory multiple myeloma. Studies are ongoing in NHL and chronic lymphocytic leukemia. G3139, an antisense oligonucleotide, has shown promise in early studies. Rituximab has revolutionized the treatment of NHL. However, other active antibodies are now available, including alemtuzumab, epratuzumab, and Hu1D10. The radioimmunoconjugates (90)Y-ibritumomab tiuxetan and (131)I-tositumomab may also play an important role in the management of NHL. Future therapeutic strategies should involve rational combinations of new chemotherapy drugs, biologic agents, and antisense compounds to increase the cure rate in patients with lymphoma.
authors.affiliation: Clinical Investigations Branch, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Cheson
mesh_terms: D000227:Adenine Nucleotides; D000074323:Alemtuzumab; D000470:Alkaloids / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001087:Arabinonucleosides / Q000627:therapeutic use; D000069461:Bendamustine Hydrochloride; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000077866:Clofarabine; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004148:Dioxolanes / Q000627:therapeutic use; D005419:Flavonoids / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D009101:Multiple Myeloma / Q000188:drug therapy; D016328:NF-kappa B / Q000187:drug effects; D009588:Nitrogen Mustard Compounds / Q000627:therapeutic use; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D010447:Peptide Hydrolases / Q000187:drug effects; D010880:Piperidines / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use; D046988:Proteasome Endopeptidase Complex; D011719:Pyrazines / Q000627:therapeutic use; D012074:Remission Induction; D000069283:Rituximab; D019311:Staurosporine / Q000031:analogs & derivatives; D013873:Thionucleotides / Q000627:therapeutic use
chemical_list: D000227:Adenine Nucleotides; D000470:Alkaloids; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D001897:Boronic Acids; D004148:Dioxolanes; D005419:Flavonoids; D018796:Immunoconjugates; D016328:NF-kappa B; D009588:Nitrogen Mustard Compounds; D016376:Oligonucleotides, Antisense; D010880:Piperidines; D011480:Protease Inhibitors; D011719:Pyrazines; D013873:Thionucleotides; C448700:epratuzumab; D000074323:Alemtuzumab; C077990:alvocidib; D000069283:Rituximab; C074908:troxacitabine; D000069286:Bortezomib; D000077866:Clofarabine; C054852:7-hydroxystaurosporine; C408162:oblimersen; D003596:Cytosine; D000069461:Bendamustine Hydrochloride; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C448699:apolizumab; D019311:Staurosporine