Bevacizumab (Avastin) in Advanced Prostate Cancer
Walter Sall, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 14, 2003
Faculty Disclosure: Joel Picus, MD
This presentation by Dr. Picus discusses the use of bevacizumab in the treatment of prostate cancer which has not been approved by the FDA.
Presenter: Joel Picus, MD
Affiliation: Washington University School of Medicine
Hormone refractory prostate cancer has a very aggressive natural history with reported median survival as low as 10-12 months. Accepted chemotherapeutic regimens include mitoxantrone/prednisone and docetaxel(Taxotere)/estramustine. Mitoxantrone regimens provide effective palliation but do not improve survival. Results are pending of a recent Intergroup trial comparing mitoxantrone and docetaxel based regimens. Docetaxel as a single agent has been shown to result in 50% or greater PSA reduction in 46% of patients at Washington University.
The combination of docetaxel and estramustine holds much promise. Both have microtubule activity with synergistic in vitro anti-tumor activity. The recent CALGB docetaxel/estramustine trial showed 69% of patients had a greater than 50% PSA reduction.
Bevacizumab is a humanized murine monoclonal antibody to vascular endothelial growth factor(VEGF). VEGF has been shown to be an important tumor growth factor in many, if not most cancers. VEGF has been shown to be upregulated in prostate cancer with levels correlating with survival.
In a single-arm, phase II CALGB trial, hormone refractory prostate cancer patients with documented metastatic disease received estramustine, docetaxel and bevacizumab. Premedication with decadron was required with coumadin recommended. Controversy exists regarding the utility of anti-coagulation in these patients receiving both estramustine (with its thrombosis risk) and bevacizumab (with its bleeding risk). Primary trial endpoints were time to progression (TTP) and response rate (RR).
79 patients were enrolled from October 2001 to October 2002. To date, PSA progression has been documented in only 29/75 patients with median time to PSA progression of 10.3 months. 77% of patients had at least a 50% reduction in PSA. Of patients with measurable disease, 44% had a PR and 32% had stable disease. No survival data are available yet. One death due to mesenteric vein thrombosis has been seen. Two non-lethal PEs and 2 DVTs have occurred.
In conclusion, Bevacizumab has been shown to be safe when administered with docetaxel and estramustine with encouraging disease response rate. There does not appear to be any additional toxicity due to the addition of bevacizumab. Long term survival and progression data are eagerly awaited from this recently completed trial.