HOUSTON, February 27, 2009 – Dr. Guru Sonpavde, a genitourinary cancer researcher affiliated with the US Oncology Research network, presented findings from a Phase II clinical study testing azacitidine in castration-resistant prostate cancer progressing on combined androgen blockade.  

The findings were presented at the 2009 Genitourinary (GU) Cancers Symposium
February 26-28 in Orlando by physicians affiliated with US Oncology, Inc.  US Oncology supports one of the nation’s largest health care services networks focused exclusively on cancer treatment and research. This trial also involved a collaboration with basic researchers at the M.D. Anderson Cancer Center to perform correlative pharmacodynamic studies on the plasma DNA of all patients. 
 
“The toxicity profile was excellent,” said Dr. Sonpavde, of Texas Oncology – Deke Slayton Cancer Center, a US Oncology-affiliated practice. “Given the biologic activity and tolerability, azacitidine may warrant further evaluation in men with castration-resistant prostate cancer.”

Dr. Sonpavde’s study “Phase II study of azacitidine for castration-resistant prostate cancer (CRPC) progressing on combined androgen blockade (CAB),” was designed to primarily determine whether azacitidine would demonstrate anti- tumor activity as measured by an increase in PSA-doubling time (DT),  with the secondary endpoints being PSA response, clinical progression-free survival (PFS) and the toxicity profile. Preclinically, hypomethylating agents reverse the resistance of prostate cancer to androgen ablation. Azacitidine is a hypomethylating agent that activates genes repressed by promoter methylation. This was a biomarker-driven phase II clinical trial evaluating azacitidine for patients with chemonaive CRPC progressing on combined androgen blockade with a rapid PSA doubling time (DT) of <3 months. Thirty-six patients were accrued with the majority (80.6%) having metastatic disease.

The trial demonstrated biologic activity for azacitidine, with 55.8% attaining the primary endpoint of increasing the PSA-DT to ≥3 months. Also, 1 patient achieved ≥30% PSA decline, which suggests a favorable disease-modifying effect.

Additionally, prolongation of PSA-DT was shown to correlate with a decrease in plasma DNA methylation suggesting the biologic hypomethylation by azacitidine may translate into clinical activity.  A subset of patients also achieved prolonged clinical progression-free survival, suggesting anti-tumor activity.

Results from this trial suggest that the anti-tumor and favorable disease-modifying activity for azacitidine may  partly be attributed to its hypomethylating mechanism. Given its favorable tolerability profile, development of combinations with other biologic and chemotherapeutic agents may be warranted.

The researchers on this trial were Guru Sonpavde1,2,  Ana Aparicio 3, Robert Delaune1,4, Lawrence E. Garbo 1,5, Feng Zhan1, Lianchun Xiao3, Kristi A. Boehm 1, Lina Asmar1,  and Daniel D. Von Hoff 1,6  .

1US Oncology Research, Inc., Houston, TX; 2Texas Oncology, P.A., Webster, TX; 3University of Texas M.D. Anderson Cancer Center, Houston, TX; 4Minnesota Hematology Oncology, St. Paul, MN; 5New York Oncology Hematology, Albany, NY; 6Translational Genomics Research Institute (TGen), Phoenix, AZ

The US Oncology Research network presents at major conferences throughout the year. Most recently, Dr. Donald Richards, a principal cancer researcher affiliated with the network, presented “Phase  II randomized study of gemcitabine (G) plus enzastaurin (E) or single-agent gemcitabine in locally advanced or metastatic pancreatic cancer,” at the ASCO Gastrointestinal Cancers Symposium in San Francisco, California, held January 15-17,2009. 

About Epigenetics
Azacitidine is believed to exert its antineoplastic effects by multiple mechanisms including cytotoxicity on abnormal haematopoietic cells in the bone marrow and hypomethylation of DNA. The cytotoxic effects of azacitidine may result from multiple mechanisms, including inhibition of DNA, RNA and protein synthesis, incorporation into RNA and DNA, and activation of DNA damage pathways. Non proliferating cells are relatively insensitive to azacitidine. Incorporation of azacitidine into DNA results in the inactivation of DNA methyltransferases, leading to hypomethylation of DNA. DNA hypomethylation of aberrantly methylated genes involved in normal cell cycle regulation, differentiation and death pathways may result in gene re expression and restoration of cancer suppressing functions to cancer cells. The relative importance of DNA hypomethylation versus cytotoxicity or other activities of azacitidine to clinical outcomes has not been established.

About US Oncology Research
The US Oncology Research network is an established community-based research operation specializing in comprehensive Phase I-IV trials and translational Phase I research. The research network is currently enrolling patients at 109 research sites, and is involved in 63 open trials.
Supported by US Oncology, the network has played a pivotal role in 24 of the last 30 cancer drugs approved by the Food and Drug Administration and more than 32,000 patients have participated in clinical trials. For more information, visit the "Research" section under "Our Services" on the company's Web site, www.usoncology.com.

About US Oncology
US Oncology, headquartered in Houston, works closely with physicians, manufacturers and payers to identify and deliver innovative services that enhance patient access to advanced cancer care. US Oncology supports one of the nation’s foremost cancer treatment and research networks, accelerating the availability and use of evidence-based medicine and shared best practices.

US Oncology’s expertise in supporting every aspect of the cancer care delivery system—from drug development to treatment and outcomes measurement—enables the company to help increase the efficiency and safety of cancer care. According to the company’s last quarterly earnings report, US Oncology is affiliated with 1,227 physicians operating in 485 locations, including 92 radiation oncology facilities in 39 states. For more information, visit the company’s Web site, www.usoncology.com.
 
# # #

Editor’s Note:  For the study abstracts, please contact Lisa Henderson at lisa.henderson@hillandknowlton.com.