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Oral drug perifosine is safe to treat metastatic colon cancer: Keryx, AEterna Zentaris

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Friday, January 22, 2010, 13:13 This news item was posted in Clinical Trials category and has 0 Comments so far.

Perifosine does not causeĀ  hair-loss, a common toxic effect with leading cancer drugs

Perifosine (KRX-0401), a first-in-class oral drug is foud effective and safe to treat metastatic colon cancer in combination with capecitabine in a crucial phase of clinical trials.

The clinical data to be presented demonstrates the potential safety and efficacy of perifosine in the treatment of patients with metastatic colon cancer, Keryx Biopharmaceuticals announced.

Perifosine (KRX-0401) is a novel oral anti-cancer agent that modulates Akt, and a number of other key signal transduction pathways, including the JNK and MAPK pathways, all of which are pathways associated with programmed cell death, cell growth, cell differentiation and cell survival.

The effects of Perifosine (KRX-0401) on Akt are of particular interest because of the importance of this pathway in the development of most cancers, with evidence that it is often activated in tumors that are resistant to other forms of anticancer therapy, and the difficulty encountered thus far in the discovery of drugs that will inhibit this pathway without causing excessive toxicity.

High levels of activated Akt (pAkt) are seen frequently in many types of cancer and have been correlated with poor prognosis.

Over 1,800 patients have been treated with perifosine (KRX-0401) in trials conducted both in the United States and Europe, so far.

Perifosine (KRX-0401)’s safety profile is distinctly different from that of most cytotoxic agents.

Perifosine (KRX-0401) does not appear to cause flu-like symptoms, thrombocytopenia (decrease in platelets that may result in bleeding) or alopecia (hair loss); all of these toxicities occur frequently with many of the currently available treatments for cancer.

The main side effects of perifosine (KRX-0401) are nausea, vomiting, diarrhea and fatigue, but these are generally well-managed particularly at lower daily doses (50 mg or 100 mg) that have induced tumor regression. Responses have been seen with both daily and weekly regimens. At the doses studied, the daily regimens were better tolerated.

Keryx has conducted seven Phase 1 single agent studies of perifosine (KRX-0401), three in Europe by Zentaris and four in the United States by the NCI, a department of the National Institutes of Health, or NIH, as part of a Cooperative Research and Development Agreement, or CRADA.

Thirteen Phase 1/2 studies of perifosine (KRX-0401) in combination with other drugs have been conducted by Keryx.

Agents that have been included in these combinations include gemcitabine, paclitaxel, docetaxel, prednisone, doxorubicin, capecitabine, pemetrexed, irinotecan, Doxil (doxorubicin HCl liposome injection), trastuzumab, various endocrine therapies, imatinib, bortezomib, lenalidomide, sorafenib, and sunitinib.

Perifosine (KRX-0401) has generally been well tolerated when used as a low daily dose (50 mg or 100 mg) in combination with these approved agents.

Perifosine (KRX-0401) has also been studied in combination with radiotherapy without evidence of increased toxicity.

The NCI has completed a number of Phase 2 clinical trials studying perifosine (KRX-0401) as a single agent, including studies in prostate, breast, head and neck and pancreatic cancers, as well as melanoma and sarcomas. In total, nine NCI clinical trials have been conducted across these six tumor types, Keryx said.

KRX-0401 has also been evaluated in ten Phase 2 clinical studies conducted by Keryx evaluating the single agent activity in various tumor types where patients have progressed on standard treatments.

Clinical trials where responses have been reported have been conducted in patients with renal cell carcinoma, advanced brain tumors, soft-tissue sarcomas, hepatocellular carcinoma, as well as in hematologic malignancies including multiple myeloma and Waldenstrom’s macroglobulinemia.

Keryx partners with AEterna Zentaris Inc, a late-stage drug development company specialized in oncology and endocrinology, on the development and commercialization of perifosine.

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