Inhibiting Angiogenesis in Metastatic Castration-Resistant Prostate Cancer
Name of the Trial
A Phase 2 Trial of Bevacizumab, Lenalidomide, Docetaxel, and Prednisone (ART-P) for Treatment of Metastatic Castrate-Resistant Prostate Cancer (NCI-09-C-0195). See the protocol summary.
Dr. William Dahut, NCI Center for Cancer Research
Why This Trial Is Important
Men with advanced prostate cancer often receive treatment to block the production of androgens, which are male sex hormones that may help prostate tumors grow. However, prostate cancers that initially respond to antiandrogen therapy eventually develop the ability to grow without androgens. Such cancers are often referred to as hormone refractory, androgen independent, or castration resistant. Metastatic castration-resistant prostate cancer (mCRPC) is usually treated with the chemotherapy drug docetaxel and the steroid prednisone.
The development of new blood vessels, or angiogenesis, is thought to be an important factor in prostate cancer progression. In an effort to extend the survival of men with mCRPC, doctors are exploring the possibility of combining agents that target angiogenesis with docetaxel and prednisone. The monoclonal antibody bevacizumab (Avastin) is an angiogenesis inhibitor that has been studied in numerous types of cancer, including prostate cancer. In a previous clinical trial, the combination of bevacizumab and docetaxel was active and well tolerated in patients with mCRPC. A recent study by NCI researchers showed that adding another antiangiogenic drug, thalidomide, to this combination, along with prednisone, improved survival well beyond what is typically seen in these patients. This improvement, however, came with increased side effects, including fatigue, neuropathy, and suppression of bone marrow function. In an attempt to maintain the activity of this combination while reducing its associated side effects, the NCI research team is replacing thalidomide with a structurally similar drug, lenalidomide (Revlimid).
In this trial, patients with mCRPC who have received no treatment for metastatic disease will be treated with docetaxel, prednisone, bevacizumab, and lenalidomide. The researchers want to find out whether lenalidomide can be safely added to the other drugs and determine the extent to which the patients’ prostate cancer responds to the combined treatment.
“We’ve shown that targeting tumor angiogenesis through two different mechanisms—using bevacizumab and thalidomide—in addition to docetaxel chemotherapy helps patients live longer than one would expect using standard chemotherapy alone,” said Dr. Dahut. “Now we want to see if we can safely replace thalidomide with lenalidomide, which is usually well-tolerated in patients with solid tumors, and still produce the kind of results we’ve seen with thalidomide.
“Ultimately, if the regimen proves safe and effective, we hope that it will offer a life-extending treatment option to men with metastatic castration-resistant prostate cancer,” he added.