Expert review of anticancer therapy
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Expert Rev Anticancer Ther · Aug 2006
ReviewRituximab for the treatment of diffuse large B-cell lymphomas.
For more than 25 years, the combination of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) was considered the gold standard for the treatment of aggressive lymphomas, 90% of which are diffuse, large B-cell lymphomas (DLBCLs). Attempts to improve results by more intensive chemotherapy regimens, including high-dose chemotherapy approaches necessitating stem-cell support, have not convincingly shown improved outcome of DLBCL. The chimeric monoclonal antibody rituximab, which binds to the CD20 antigen expressed on normal B cells and the malignant cells of more than 90% of DLBCLs, and mediates lysis of these cells by direct induction of apoptosis, activation of complement- and antibody-dependent cellular cytotoxicity in vitro, is an attractive candidate for the treatment of B-cell lymphomas. ⋯ Questions remain concerning the optimal dosage and schedule of rituximab for DLBCL, as well as the optimal chemotherapy regimen partner for rituximab. Rituximab is the first monoclonal antibody to consistently improve survival rates of patients with a malignant disease. Its excellent efficacy in combination with cytotoxic chemotherapy, together with its favorable toxicity profile, establishes rituximab as an indispensable component of modern standard immunochemotherapy of DLBCL.
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Expert Rev Anticancer Ther · Aug 2006
ReviewTemozolomide: a milestone in neuro-oncology and beyond?
Temozolomide (Temodal, Temodar), an imidazol derivative, is a second-generation alkylating agent. The orally available prodrug with the capacity of crossing the blood-brain barrier received accelerated US FDA approval in 1999. Three pivotal Phase II trials showed modest activity in the treatment of recurrent anaplastic astrocytoma glioblastoma. ⋯ Continuous temozolomide administration is associated with profound CD4-selective lymphocytopenia. Molecular studies have suggested that the benefit of temozolomide chemotherapy is restricted to patients whose tumors have a methylated methylguanine methyltransferase gene promotor and are thus unable to repair some of the chemotherapy-induced DNA damage. Temozolomide is under investigation for other disease entities, in particular lower-grade glioma, brain metastases and melanoma.