Avastin for prostate cancer – pro

Lay Summary: A great deal of clinical investigation of Avastin for prostate cancer is ongoing but little is as of yet securely known.

Drugs used in chemotherapy, such as docetaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether docetaxel, prednisone and bevacizumab are more effective than docetaxel and prednisone in treating prostate cancer.

Findings from a recent phase II trial have shown that a combination of provange and avastin may be beneficial for patients with prostate cancer. The study population consisted of 22 patients who had androgen depended prostate cancer and was having increasing levels of PSA. All patients had undergone previous definitive treatment either in the form of radiation therapy or surgery. All patients received a combination of APC8015 (provenge) in combination with avastin. The treatment was continued until patient had either disease progression or intolerable side effects. The FDA followed ODAC’s recommendation against Provenge.

Out of 22 patients 21 were evaluable for end points of the study. The median PSA doubling time in these patients was 6.7 months and median time on treatment was 12.7 months. No patients on the study had objective disease progression (onset of measurable bone or soft tissue metastasis). Four patients could not continue with the study due to toxicities and were removed from the study.

The results of a CALGB trial indicate that Avastin™/Taxotere® and estramustine can be administered safely and effectively in patients with hormone-refractory prostate cancer. The median age of the patients in this trial was 73 years, and the median PSA at study entry was 128 ng/dl. Of the 79 evaluable patients treated, 45% had measurable soft tissue lesions while 85% had a positive bone scan. Thromboembolic events (6%) were reported in 5 patients; one patient succumbed to a pulmonary embolus. Measurable disease responses were observed and 42% of patients, while 79% of patients evidenced a >50 percent PSA decline. The median time to progression has not yet been reached, and the median survival reported was approximately 20 months. The rate of thromboembolic events with this combination appears to be similar to what has been reported for other estramustine/taxane studies. Avastin alone is in a phase II trial.

There is an ongoig randomized phase III trial that is studying docetaxel, prednisone and bevacizumab to see how well they work compared to docetaxel and prednisone in treating patients with prostate cancer that did not respond to hormone therapy. Other combination trials are also being launched.

http://www.slhn-lehighvalley.org/body.cfm?id=700#CTSU90401

http://www.clinicaltrials.gov/ct/gui/show/NCT00089609

Picus J, Halabi S, Rini B, et al. The use of bevacizumab (B) with Taxotere (D) and estramustine (E) in hormone refractory prostate cancer (HRPC): Initial results of CALGB 90006. Proceedings from the 39th annual meeting of the American Society of Clinical Oncology, May 2003.Abstract 1578.

nccn.org, prostate

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