A Single-center Retrospective Analysis of the Effect of Radium-223 (Xofigo) on Pancytopenia in Patients with Metastatic Castration-resistant Prostate Cancer

Abstract

Introduction Radium-223 (Xofigo, Bayer Pharmaceuticals Inc., Whippany, NJ) has been shown to increase overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC), via the phase 3 ALpharadin in SYMPtomatic Prostate CAncer (ASLYMPCA) study. Hematologic side effects of radium-223 included all-grade anemia in 31% of the patients, thrombocytopenia in 12%, and neutropenia in 5%, and persistent pancytopenia noted in 2%. However, the incidence seen in our institutional clinical practice is higher than that reported in the literature. Methods A retrospective analysis was performed by analyzing patients with mCRPC who received Xofigo at the University of Florida Health Shands Hospital (UF Health Shands) in a three-year span. Data collected included complete blood count (CBC), ECOG (Eastern Cooperative Oncology Group) functional status, kidney and liver function, evidence of bony disease on imaging, prior chemotherapy regimens, total radiation dose, and prostate-specific antigen (PSA). Results Twenty-three patients received Xofigo at UF Health, and one was lost to follow-up. Sixteen patients (73%) completed the full course (six doses) of Xofigo, while six did not. Ten patients (45%) developed pancytopenia, with two recovering counts within eight months while the other eight had persistent cytopenias (six of which were transfusion-dependent). Older age and higher ECOG score correlated with increased risk of pancytopenia. In addition, a higher percentage of patients who received prior radiation therapy were more likely to develop pancytopenia (90% vs 75%). Conclusions We found a higher rate of Xofigo-induced pancytopenia in our patient population than the 2% reported in the literature, albeit with a limited sample size, This may influence clinical decision making in the treatment of mCRPC, as pancytopenia may preclude patients from other survival-prolonging therapies. Factors such as age, functional status, and prior radiation therapy have to be considered prior to Xofigo treatment.

Commercial and business aspects of alpha radioligand therapeutics

“…First developed by Algeta and later by Bayer following a $2.9 billion acquisition, 223 Ra-dichloride was designed to treat metastatic castration-resistant prostate cancer (mCRPC). In its pivotal ALSYMPCA Phase III trial, the compound resulted in a 30% reduction in the risk of death compared with placebo, and extended patient lives by a median of 14 months compared to 11.2 months ( 41 , 42 ).…”

“…In 2018, Xofigo suffered a double-digit sales decline that continued for several years ( Figure 3 ), exacerbated by COVID-19 restrictions ( 45 ). Despite the challenges, Xofigo remains an approved therapy for the treatment of prostate cancer and 223 Ra-chloride is undergoing further evaluation in several ongoing trials; the commercial performance of Xofigo has far exceeded those of the beta-emitters Zevalin and Bexxar ( 42 ).…”

Cutting edge rare earth radiometals: prospects for cancer theranostics

“…Alpha radionuclides have garnered significant interest in nuclear medicine due to their ability to deliver a high radiation dose to tumours. This property has allowed for the treatment of a variety of diseases including neuroendocrine tumours (Navalkissoor and Grossman 2019 ) and, most successfully, prostate cancer with bone metastases (Skelton et al 2020 ). The alpha emitting radionuclides most used in these treatments ( 225 Ac, 223 Ra) have alpha emitting daughter products.…”

Characterization of a segmented printed circuit board (PCB) as a standard for absorbed dose to water from alpha‐emitting radionuclides

“…[1][2][3][4] Recently, FDA approval was granted for an alpha-emitting radionuclide for the treatment of castration-resistant metastatic prostate cancer. 5 Alpha particle-labeled microspheres are currently being investigated for treatment of colorectal cancers. 6 Brachytherapy with alpha particles is also gaining popularity due to the emergence of diffusing alpha-emitter radiation therapy (DART).…”

“…Targeted radionuclide therapy (TRT) using alpha particles is an emerging treatment technique leveraging the shorter range and higher linear energy transfer (LET) of alpha particles in tissue when compared to beta particles 1–4 . Recently, FDA approval was granted for an alpha‐emitting radionuclide for the treatment of castration‐resistant metastatic prostate cancer 5 . Alpha particle‐labeled microspheres are currently being investigated for treatment of colorectal cancers 6 .…”