May 20, 2006: Daniel Shevrin, M.D.
New "Targeted" Agents in Prostate Cancer
1. Erlotinib (Tarceva) is a "targeted" drug which targets the EGF receptor. It is active in  lung cancer and pancreatic cancer and has been approved for use in these tumors. There  is growing evidence that activation of EGF and its various "downstream" signal transduction  pathways and proteins may activate the androgen receptor and contribute to progression  of prostate cancer in a "castrate" environment. I am specifically investigating the activity  of this drug in a Phase 2 setting (all pts get the drug) in men with prostate cancer with a  rising PSA on hormone therapy and without metastasis. The primary endpoint is effect on  PSA. The drug has relatively few side-effects. The study is supported by Genentech who  is providing the drug. There are several lab correlates that only require analysis of  prostate tissue from previous biopsy or surgery.
2. Bevacizumab (Avastin) is a "targeted" drug that targets VEGF (vascular endothelial  growth factor) which is responsible for tumor angiogenesis. This drug has proven activity  when given in conjunction with chemotherapy in colon and lung cancer. This drug may  work by improving the effectiveness of chemotherapy as well as inhibiting blood supply to  the tumor tissues. We are testing this drug in combination with Taxotere in a randomized  Phase 3 study.
3. Lepatinib is a new "targeted" drug that targets 2 proteins in the Her family (Her 1 and  2). The most well-known inhibitor of Her2 is Herceptin which is active in breast cancer.  This new drug is being tested in men with prostate cancer who have a PSA recurrence  after primary therapy and who are not on hormone therapy. Men must have a PSA with a  relatively rapid doubling time.