Hematologic Safety of Radium-223 Dichloride: Baseline Prognostic Factors Associated With Myelosuppression in the ALSYMPCA Trial

Myelosuppression is common in patients with progressive castration-resistant prostate cancer and bone metastases. Radium-223 prolongs overall survival in these patients but may cause myelosuppression; understanding risk factors will improve clinical decision making. We describe hematologic safety of radium-223 in ALSYMPCA and post hoc analyses identifying patients at increased risk for hematologic toxicity.

Hematologic parameters and adverse events were analyzed. Multivariate analyses assessing baseline risk factors for hematologic toxicities were performed separately for radium-223 and placebo patients.

Nine hundred one patients received radium-223 (n = 600) or placebo (n = 301); 65% of radium-223 and 48% of placebo patients had the full 6 cycles. Grade 3/4 thrombocytopenia was more common in radium-223 versus placebo patients (6% vs. 2%). Logistic regression analyses identified significant baseline predictors for grade 2-4 hematologic toxicities related to radium-223 treatment: extent of disease (6-20 vs. < 6 bone metastases; odds ratio [OR] = 2.76; P = .022) and elevated prostate-specific antigen (OR = 1.65; P = .006) for anemia; prior docetaxel (OR = 2.16; P = .035), decreased hemoglobin (OR = 1.35; P = .008), and decreased platelets (OR = 1.44; P = .030) for thrombocytopenia. Neutropenia events were too few in placebo patients for a comparative analysis. There were no significant associations between hematologic toxicities and number of radium-223 injections received (4-6 vs. 1-3).

Radium-223 has a favorable safety profile with a low myelosuppression incidence. Understanding baseline factors associated with myelosuppression may assist clinicians in avoiding severe myelosuppression events with radium-223.

Clinical genitourinary cancer. 2016 Aug 08 [Epub ahead of print]

Nicholas J Vogelzang, Robert E Coleman, Jeff M Michalski, Sten Nilsson, Joe M O'Sullivan, Christopher Parker, Anders Widmark, Marcus Thuresson, Lei Xu, Joseph Germino, Oliver Sartor

Comprehensive Cancer Centers of Nevada, Department of Medical Oncology, Las Vegas, NV. Electronic address: ., Weston Park Hospital, Department of Oncology, Sheffield, UK., Washington University School of Medicine, Radiation Oncology, St Louis, MO., Karolinska University Hospital, Department of Oncology, Stockholm, Sweden., Queen's University, Centre for Cancer Research and Cell Biology, Belfast, UK., Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Academic Urology Unit, Sutton, UK., Umeå University, Department of Radiation Sciences, Umeå, Sweden., Statisticon AB, Biostatistics Department, Uppsala, Sweden., Bayer HealthCare Pharmaceuticals, Global Medical Affairs Oncology, Whippany, NJ., Bayer HealthCare Pharmaceuticals, US Medical Affairs Oncology, Whippany, NJ., Tulane Cancer Center, Departments of Medicine and Urology, New Orleans, LA.