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Copies of these abstracts, which highlight the observed clinical andpreclinical activity of KRX-0401 as a single agent and in combination withnovel agents are currently available and can be viewed on-line through theASCO website: http://www.asco.org/ASCO/Abstracts+%26+Virtual+Meeting/Abstracts
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The following abstract will be available for viewing during the postersession taking place tomorrow, Tuesday, June 3, 2008, from 8:00am-12:00pm:
Abstract 8546: A Phase 2 trial of the novel oral Akt inhibitor perifosinein relapsed and/or refractory Waldenstrom macroglobulinemia
Investigators: Irene M. Ghobrial, X. Leleu, N. Rubin, R. Leduc, S. Chuma,M. Nelson, P. G. Richardson, S. P. Treon, K. C. Anderson
Following the poster session, lead investigator, Dr. Irene Ghobrial, willbe presenting the abstract during the Lymphoma and Plasma Cell DisordersPoster Discussion Forum, scheduled to take place at 12:00pm in Room E450a.
Additionally, the following abstracts have been accepted for publicationonly:
Abstract 16024: Phase 1 multicenter trial of perifosine in combinationwith sorafenib for patients with advanced cancers including renal cellcarcinoma.
Investigators: M. T. Schreeder, R. A. Figlin, J. J. Stephenson, L. Campos,S. P. Chawla, D. R. Spigel, A. Spira
Abstract 14565: Phase 1 report from a multicenter trial of perifosine(PERI) + sunitinib (SUT) in patients with advanced cancers including renalcell carcinoma.
Investigators: P. Allerton, B. Ebrahimi, M. T. Schreeder, P. Kaiser, S. P.Chawla
Abstract 16083: Preclinical rationale for combination targeted therapy inadvanced clear cell renal cell carcinoma (RCC): Abrogation ofrapamycin-mediated induction of AKT phosphorylation by perifosine.
Investigators: W. S. Holland, P. C. Mack, D. R. Gandara, P. N. Lara
KRX-0401 (Perifosine) Mechanism of Action and Profile
KRX-0401 (Perifosine) is a novel, potentially first-in-class, oralanti-cancer agent that modulates Akt and a number of other key signaltransduction pathways, including the JNK and MAPK pathways, all of which arepathways associated with programmed cell death, cell growth, celldifferentiation and cell survival. The effects of perifosine on Akt are ofparticular interest because of the importance of this pathway in thedevelopment of most cancers, the evidence that it is often activated in tumorsthat are resistant to other forms of anticancer therapy, and the difficultyencountered thus far in the discovery of drugs that will inhibit this pathwaywithout causing excessive toxicity. High levels of activated Akt (pAkt) areseen frequently in many types of cancer and have been correlated with poorprognosis in patients with soft-tissue sarcoma, gastric, hepatocellular,endometrial, prostate, renal cell, head and neck cancers and hematologicalmalignancies, as well as glioblastoma. The majority of tumors expressing highlevels of pAkt were high-grade, advanced stage or had other featuresassociated with poor prognosis. High pAkt is often seen in tumors that areresistant to conventional cancer treatments, including radiotherapy,chemotherapy, endocrine therapy, and especially therapy with some of the newerbiologicals.
To date, over 1,700 patients have been treated with KRX-0401 in trialsconducted both in the United States and Europe. Its safety profile isdistinctly different from that of most cytotoxic agents. It does not appear tocause myelosuppression (depression of the immune system that may lead to lifethreatening infections), thrombocytopenia
