Pancreatic cancer is one of the most lethal malignancies in the US. The primary curative treatment is surgery and is only appropriate for approximately 20% of presenting patients because most will present with locally invasive or metastatic disease. Although Gemcitabine has been proven superior to 5-Fluoracil in advanced pancreatic cancer, long term survival is rarely seen. Other agents are clearly needed to treat this refractory disease. Strong evidence points to the importance of raf kinases in the development and maintenance of human cancers. For example, raf proteins have been demonstrated to be direct downstream effectors of ras protein functions within the MAP kinase signaling pathway. Since 75% of patients with pancreatic cancer have ras mutations, novel therapy directed against raf kinases are particularly exciting in this malignancy. ISIS 5232 is a phosphorothioate oligonucleoide antisense inhibitor of human c-raf kinase or are in an expression in-vivo and in-vitro. This is a limited institution ECOG phase II trial which will look at the response rates and toxicity of ISIS 5132 administered by continuous infusion via portable pump (provided free of charge). Numerous samples for pharmocokinetics and measuring of downstream effects will be needed during the course of this trial. This novel therapy has numerous avenues for future theraputic directions, including adjuvant therapy or perhaps combination therapy with other standard chemotheraputic agents.
Showing the most recent 10 out of 767 publications
