preliminary reports from the amount of phase I trials invest

Initial reports from a number of phase I studies examining the mix of perifosine with conventional cytotoxic chemotherapeutic agents such as for example taxanes and gemcitabine suggest that these combinations could be safely administered. Dizocilpine is a logical target for perifosine combination therapy based on in vitro data where perifosine triggers cytotoxicity in MM cell lines and individual MM cells resistant to conventional therapy. Perifosine also shows antitumor activity in a human plasmacytoma mouse model. Preliminary results from the phase II study of perifosine alone or in mixture with dexamethasone for patients with relapsed or refractory MM said that single agent perifosine induced stabilization of disease in 6 of 25 evaluable patients. A minor response was conferred by the addition of dexamethasone to perifosine in patients who progressed on perifosine monotherapy in three of nine evaluable patients and stabilization of infection in two of nine patients. Based upon the promising task of perifosine as just one agent and Cellular differentiation in combination with dexamethasone, further reports of perifosine in MM using different dosing schedules in addition to in combination with the proteosome inhibitor bortezomib are in the pipeline. In the 1980s and 1990s, a number of stage I and II clinical trials were done utilizing triciribine as a cytotoxic agent in a variety of sophisticated malignancies at different dosing schedules. Small effectiveness was seen with few objective responses, and triciribine at high doses caused a number of severe toxicities, including hepatotoxicity, hyperglycemia and hypertriglyceridemia. If the hyperglycemia and hypertriglyceridemia were linked to inhibition of Akt 2 is as yet not known. In these tests, pharmacokinetic research revealed irregular drug degrees of triciribine, especially with a day continuous infusion dosing schedule. With the recent development of triciribine as a bona fide Akt inhibitor, phase I clinical trials are underway utilizing lower amounts of triciribine phosphate by weekly IV infusions order Canagliflozin in patients with metastatic strong tumors whose tumors carry large expression of phospho AKT as well as in patients with myeloid malignancies. In inclusion, tests incorporating triciribine phosphate with tyrosine kinase inhibitors such as for example erlotinib and lapatinib to overcome secondary and primary resistance mechanisms to ErbB family inhibitors are currently in development. The mTOR inhibitors, CCI 779 and RAD 001, have been tested as single agents in phase II trials in many different tumor types, and objective responses and stabilization of disease have been noted in breast cancer, glioblastoma, neuroendocrine carcinoma, renal cell carcinoma, mantle cell lymphoma, and myeloid malignancies.

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