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Anti-angiogenesis drugs thalidomide & bevacizumab


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Written by Christopher P. Evans, MD

Monday, 05 July 2010

BERKELEY, CA (UroToday.com) - In the April 20, 2010 issue of the Journal of Clinical Oncology, Dr. Yang-Min Ning and collaborators report a Phase II trial combining chemotherapy with anti-angiogenesis drugs for men with castration-resistant prostate cancer (CRPC). The data suggests that such a combination is more effective than chemotherapy alone.

The studies used docetaxel, now the standard chemotherapy for CRPC. The two anti-angiogenesis drugs were thalidomide and bevacizumab. Thalidomide inhibits basic fibroblast growth factor, endothelial cell proliferation, circulating endothelial cells, and expression of tumor necrosis factor-alpha. Bevacizumab blocks VEGF. Due to the different mechanisms, the investigators hypothesized that the combination would have an additive effect with docetaxel. The treatment groups for the mouse androgen-independent PC3 cell xenograft model were each drug alone, docetaxel combined with thalidomide, docetaxel with bevacizumab, or docetaxel with thalidomide and bevacizumab. Compared with control mice, PC3 tumor growth was decreased 16% by either thalidomide or bevacizumab alone. Both of these agents together had no further inhibitory effect. Docetaxel alone reduced tumor volume by 52% after 2 weeks of treatment, and combination with thalidomide or bevacizumab was not significantly different. However, using all 3 drugs together resulted in a 71% reduction in tumor volume.

Among the 60 patients enrolled in the single arm (all three drugs combined) phase II study, 6 remained on study at the time of this report. Of the remaining 54 patients, 41 had disease progression, 5 withdrew secondary to toxicity, 7 withdrew voluntarily and one died of other causes. The majority of patients required some dose modifications and all had grade 3 or 4 toxicities, primarily neutropenia. Of the 58 patients with PSA active disease, 52 (89.6%) had PSA decline >50%, 4 had PSA decline <50%, 2 had a rising PSA while on study, 44 (76%) had PSA decline >75%, and 51 (87.9%) had PSA decline >30% in the first three months of treatment. Confirmed responses included two complete and 19 partial responses. The overall response rate was 64%. Eleven men had stable disease and one had disease progression. As a secondary endpoint, progression free survival was measured and the median time to progression was 18.3 months. The median survival time for the three-drug combination was 28.2 months, while their predicted survival was 14 months. Patients with a PSA decline >75% had a significant increase in circulating apoptotic endothelial cells compared with those who had a <75% PSA decline, indicating greater anti-angiogenic activity.

Ning YM, Gulley JL, Arlen PM, Woo S, Steinberg SM, Wright JJ, Parnes HL, Trepel JB, Lee MJ, Kim YS, Sun H, Madan RA, Latham L, Jones E, Chen CC, Figg WD, Dahut WL

J Clin Oncol. 2010 Apr 20;28(12):2070-6


PubMed Abstract

PMID: 20308663 Forum: Castrate Resistant Prostate Cancer Title: Anti-angiogenesis drugs thalidomide and bevacizumab improve docetaxel chemo

This extract can be found on http://PubMed.com, and is in the public domain.

On PubMed.com there will be a link to the full paper (often $30, sometimes free).

Any highlighting (except the title) is not by the author, but by Jim Marshall.

Jim is not a doctor.

This page was found on the Advanced Prostate Cancer Community for Australian men at http://advancedprost...lia.ipbhost.com.

The link is hard to remember.

An easier way to find it is to go to JimJimJimJim.com and click on Prostate.

That's the word Jim four times, no spaces, followed by .com.

If you need other help - to perhaps find someone to talk to or a local support group:

Click on the Contact Jim button at http://JimJimJimJim.com.

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