Chemotherapy following radium-223 dichloride treatment in ALSYMPCA

BACKGROUND - Radium-223 prolongs overall survival in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases, regardless of prior docetaxel. Whether or not chemotherapy can be safely administered following radium-223 treatment is of clinical importance.

An exploratory analysis of prospectively collected data, from the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) patient subgroup who received chemotherapy after radium-223 or placebo treatment, was conducted to evaluate the safety and efficacy of chemotherapy following radium-223.

METHODS - In ALSYMPCA, CRPC patients with symptomatic bone metastases and no visceral metastases were randomized 2:1 to receive six injections of radium-223 (50 kBq/kg IV) or placebo plus best standard of care, stratified by prior docetaxel, baseline alkaline phosphatase, and current bisphosphonate use. In this exploratory analysis, chemotherapy agents administered following study treatment were identified; timing and duration were calculated. Hematologic safety was reviewed, and overall survival analyzed.

RESULTS - Overall, 142 radium-223 and 64 placebo patients received subsequent chemotherapy; most common were docetaxel (70% radium-223, 72% placebo) and mitoxantrone (16% radium-223, 20% placebo). The majority of patients (61% radium-223, 58% placebo) had received prior docetaxel. Radium-223 patients started subsequent chemotherapy later than placebo patients; chemotherapy duration was similar between groups. In radium-223 and placebo patients receiving subsequent chemotherapy, median hematologic values (hemoglobin, neutrophils, and platelets) remained nearly constant up to 18 months following start of chemotherapy, regardless of prior docetaxel treatment. A low percentage of patients in both groups had grades 3-4 hematologic values (<10%). Platelet count decline, from last measurement before chemotherapy, was numerically greater in radium-223 versus placebo patients. Median overall survivals from start of chemotherapy were 16.0 and 15.8 months following radium-223 and placebo, respectively.

CONCLUSIONS - Chemotherapy following radium-223, regardless of prior docetaxel, is feasible and appears to be well tolerated in patients with CRPC and symptomatic bone metastases. Prostate. © 2016 Wiley Periodicals, Inc.

The Prostate. 2016 Mar 23 [Epub ahead of print]

Oliver Sartor, Peter Hoskin, Robert E Coleman, Sten Nilsson, Nicholas J Vogelzang, Oana Petrenciuc, Karin Staudacher, Marcus Thuresson, Christopher Parker

Department of Medicine, Tulane Cancer Center, New Orleans, Louisiana., Marie Curie Research Wing for Oncology, Mount Vernon Hospital Cancer Centre, Middlesex, United Kingdom., Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield, Sheffield, United Kingdom., Department of Oncology, Karolinska University Hospital, Stockholm, Sweden., Department of Medical Oncology, University of Nevada School of Medicine and Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada., Department of Global Clinical Development, Bayer HealthCare Pharmaceuticals, Whippany, New Jersey., Department of Study Management Europe, Bayer AS (formerly Algeta ASA), Oslo, Norway., Department of Biostatistics, Statisticon AB, Uppsala, Sweden., Academic Urology Unit, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey, United Kingdom.