Syk Inhibitors ecommends prophylactic anticoagulation during treatment with lenalidomide

alidomide in PTCL was reported by Dueck et al. in the abstract form, in which 24 patients with mature T cell lymphomas were enrolled. ORR was 34% with no CRs. Major side effects include dose related myelosuppression fatigue, pruritus Diosmetin and rash. Deep vein thrombosis is rarely reported in trials where lenalidomide is used as a monotherapy, but the incidence is much higher when combined with dexamethasone. The FDA recommends prophylactic anticoagulation during treatment with lenalidomide. 8 Agents targeting apoptotic pathways Apoptotic pathways are intricately controlled by a balance between proapoptotic and antiapoptotic proteins . The Bcl 2 family are overexpressed in both solid tumors and hematologic malignancies and are associated with inhibition of apoptosis and chemotherapy resistance.
Small molecules that can target antiapoptotic Bcl 2 family members represent a new opportunity to affect this biology directly . The major advantage of these compounds lies in their ability to lower Idarubicin molecular weight the threshold required to induce apoptosis, making them potentially Syk hemmer complimentary to many conventional cytotoxic drugs used in the treatment of cancer. One class of new agents comes from gossypol, a natural product derived from cottonseed extracts, originally investigated in China as a male contraceptive agent. Derived analogs, such as the l isomer of gossypol, AT 101, and ABT 737 have exhibited inhibitory activity against a wide range of human carcinoma cell lines and tumor xenograft models. ABT 737 is a BH3 only mimetic capable of binding with high affinity to the prosurvival proteins Bcl XL, Bcl 2, and Bcl w, inducing Bax/Bak dependent killing .
A major limitation of ABT 737 is that it is not orally bioavailable. ABT 263, a potent, orally bioavailable Bad like BH3 mimetic has shown to be a more promising agent. In human tumor cells, ABT 263 induces Bax translocation, cytochrome c release and subsequent apoptosis. Oral administration of ABT 263 alone induces complete tumor regressions in xenograft models of Lenalidomide ic50 small cell lung cancer and acute lymphoblastic leukemia . This agent is now in clinical trials for CLL and in lymphoid malignancies. Patients are dosed on days 114 of a 21 day cycle . One patient with NK T cell lymphoma showed a 75% reduction of his skin lesions after cycle 2. The main toxicities include thrombocytopenia and elevation of LFTS.
Preliminary data confirm synergistic activity of these BH3 mimetics in combination with proteosome inhibitors in vitro and will form the basis of future trials. 9 Monoclonal psychological examination antibodies Monoclonal antibodies directed against proteins expressed on malignant T cells represent an attractive therapeutic strategy that may mimic the effects seen from rituximab in the treatment of B cell malignancies. Some of these antibodies are described below. 9.1 Anti CD52 Alemtuzumab is a recombinant DNAderived humanized monoclonal antibody that is directed against CD52, a 2128 kDa cell surface glycoprotein, which is expressed on mature lymphocytes. It is approved for use in CLL and has shown promising activity in the treatment of T cell malignancies. It is administered as an IV infusion given over 2 h. The dose has to be escalated to 30 mg give three times a week for a total of 12 weeks. Infusional reactions can be controlled .