A randomized, phase III, multi-national study, presented at fourth annual Genitourinary Cancers Symposium, being held February 2-4, 2012, at the San Francisco Marriott Marquis in San Francisco, CA, USA, shows that a novel radiation-emitting agent that targets bone ? and aimed at treating bone metastases ? both improved survival and delayed cancer-related bone problems in men with metastatic castration-resistant prostate cancer (CRPC). The agent, radium-223 chloride or Ra-223 (Alpharadin?), is the first alpha particle emitting drug developed to target bone that has been shown to improve survival in metastatic CRPC. It is being developed by the Norwegian company Algeta ASA, in a partnership with Bayer Pharma AG.

Radium-223 chloride) has a unique mode of action. The investigational agent combines a natural affinity for, and targeting of, bone metastases with the potent and localized tumor cell-killing activity of alpha-particle emission, which has minimal effects on surrounding normal cells.

Reducing adverse skeletal-related events
?As recently as two years ago, we had very few options for patients with this particularly difficult form of advanced prostate cancer,? said lead author A. Oliver Sartor, MD, Laborde Professor of Cancer Research at the Tulane University School of Medicine in New Orleans and medical director of the Tulane Cancer Center. ?Now we have a handful. But Radium-223 is the first treatment to both reduce adverse skeletal-related events (SREs) and improve survival, making this a particularly promising therapeutic option.?

Prostate cancer is considered castration-resistant when growth continues despite extremely low levels of testosterone. Radium-223 is a novel agent that directly targets bone metastases, delivering short bursts of high-energy alpha radiation. In the trial, called ALSYMPCA, Sartor and his colleagues randomized 922 patients with progressive, CRPC with bone metastases to receive Ra-223 plus best supportive care or placebo and best supportive care.

Significantly improved Overal Survival
An interim analysis of 805 patients showed that Ra-223 significantly improved median overall survival compared to placebo (14.0 months versus 11.2 months). As a result, the trial was ended early. Additionally, the time to the first SRE was significantly delayed (median time to SRE was 13.6 months vs. 8.4 months in the placebo group.

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Best supportive care involves treatment to address the symptoms of cancer, rather than to improve the overall disease outcomes; it includes therapies such as antibiotics, analgesics, radiation therapy for pain from bone metastases, and corticosteroids. SREs include bone fracture, spinal cord compression, external beam radiation to bone and bone surgery.

?These findings will help us to increasingly individualize advanced prostate cancer treatment, with a novel agent that can extend our patient?s lives,? Sartor noted.

Effectiveness of Combination
He said that further research is planned to examine the effectiveness of combining Ra-223 with other drugs. Studies are needed to determine whether Ra-223 is effective in combination with newly available immunotherapies, hormonal therapies, and chemotherapy. In addition, other investigators have already begun testing Ra-223 in patients with breast cancer who have bone metastases, and plans are underway for clinical studies of Ra-223 in other cancers.

For more information:
Sartor AO, Heinrich D, Helle SI, O’Sullivan JM, Fossa SD, Chodacki A, Demkow T, Logue JP, Seke M, Widmark A, Johannessen DC, Nilsson S, Hoskin P, Solberg A, James ND, Syndikus I, Vogelzang NJ, Gillies C. Radium-223 chloride impact on skeletal-related events in patients with castration-resistant prostate cancer (CRPC) with bone metastases: A phase III randomized trial (ALSYMPCA). Abstract # 9. Fourth Annual Genitourinary Cancers Symposium (2012)

Clinical trials:
A Phase III Study of Alpharadin(Radium-223)in Patients With Symptomatic Hormone Refractory Prostate Cancer With Skeletal Metastases (ALSYMPCA).

Also view:
Overall Survival Benefit of Radium-223 Chloride (Alpharadin) in the Treatment of Patients With Symptomatic Bone Metastases in Castration-Resistant Prostate Cancer (CRPC): A Phase III Randomised Trial (ALSYMPCA)Parker C, Heinrich D, O?Sullivan JM, Foss? S, Chodacki A, Demkow T, Cross A, Bolstad B, Garcia-Vargas J, Sartor O. Slide presentation (ECCO 16/ESMO 36, 2011)

Photo credit: 2012 Genitourinary Cancers Symposium – A Oliver Sartor, MD discusses his poster Abstract #9 during Poster Session A: Prostate Cancer at the 2012 Genitourinary Cancers Symposium (GU) meeting at the Marriott Marquis on Thursday February 2, 2012. A record 2500 attendees from around the world were on hand to learn the latest treatment and research in Genitourinary cancers from fellow physicians, researchers, health care professionals, cancer survivors and patient advocates. Photo by ? ASCO/Todd Buchanan.

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