ASCO GU 2017: Effects of Radium-223 with Docetaxel vs. Docetaxel alone on Bone Biomarkers in Patients with Bone-Metastatic Castration Resistant Prostate Cancer mCRPC: A Phase I/IIa Clinical Trial

Orlando, Florida USA (UroToday.com) According to Dr. Michael Morris, radium-223 dichloride (radium-223) is a radioactive isotope that emits low levels of alpha-particle radiation, which causes breaks in double strands of DNA that lead to cell apoptosis. Radium is a “calcium mimetic” that, like calcium, accumulates preferentially in areas of bone that are undergoing rapid turnover. In a phase-III trial called ALSYMPCA, the survival benefit of radium-223 was evaluated compared with placebo. In men with advanced prostate cancer that has become refractory to hormone treatment, radium-223 was found to increase median overall survival and decrease the time and incidence of skeletal-related events.

Dr. Morris and colleagues presented the results of their phase I/IIa clinical trial, which aimed to assess the safety and efficacy of combination radium-223 and docetaxel vs. docetaxel alone in patients with bone-metastatic castration-resistant prostate cancer. As part of the efficacy testing, bone biomarkers (tALP, P1NP, bALP, uCTX-1, and ICTP) were checked during the study to further elucidate the effects of combination therapy on bony metastatic disease pathophysiology and tumor microenvironment. The study included 46 patients, of which 33 underwent combination treatment and 13 were treated solely with docetaxel.

The median time to prostate-specific-antigen progression was longer with combination therapy than with docetaxel alone (7 vs. 5 months, P = .020). Combination therapy was also associated with greater declines in tALP and bone formation markers bALP and P1NP. With regard to safety, the combination of radium-223 and docetaxel was well-tolerated, with no greater safety concern than treatment with docetaxel alone. The most common side effect was neutropenia, which was seen in 30% of participants in the combination arm compared to 38% who received only docetaxel.

In conclusion, Dr. Morris and his associates noted that the combination of radium-223 and docetaxel is safe and appears to have added effect in bone pathophysiology, which may help explain the difference in progression-free survival. But the researchers advised that the findings should be further validated in a larger trial to confirm the association between clinical outcomes and biomarker response.

PRESENTED BY: MICHAEL MORRIS, MD, MEMORIAL SLOAN KETTERING CANCER CENTER, NEW YORK CITY

Andres F. Correa

Society of Urologic Oncology Fellow

Fox Chase Cancer Center-Temple Health from the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA

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