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The Effect of Radium-223 Therapy in Agent Orange-Related Prostate Carcinoma

Federal Practitioner. 2020 December;37(12)a:570-575 | 10.12788/fp.0062
November 6, 2020|AVAHO
Andrew Liman, MD;Rashmikant Shah, MD;Vida Passero, MD;Jocelyn Tan, MD;Hema Rai, MD;Laurie Harrold, MD;Joyce Tokarsky, CNS;Agnes Liman, MD;Vidhi Gupta, MD;Kristina Gerszten, MD
Author and Disclosure Information

Andrew Liman is Section Chief, Hematology/Oncology and Agnes Liman is a Staff Physician, Pathology and Laboratory Medicine, both at VA Central California Health Care System in Fresno. Vida Passero is Section Chief; Laurie Harrold, Jocelyn Tan, and Hema Rai are Staff Physicians; Joyce Tokarsky is a Staff Nurse Practitioner, all in the Hematology/Oncology section at VA Pittsburgh Health Care System in Pennsylvania. Rashmikant Shah, Kristina Gerszten, and Vidhi Gupta are Staff Physicians in the Radiology section at VA Pittsburgh Health Care System, Pennsylvania. at VA Central California Health Care System in Fresno. Andrew Liman is an Assistant Clinical Professor of Medicine at the University of California San Francisco at Fresno. Vida Passero, Laurie Harrold, Jocelyn Tan, and Hema Rai are Assistant Clinical Professors of Medicine at the University of Pittsburgh Cancer Institute in Pennsylvania.
Correspondence: Andrew Liman (andrew.liman@va.gov)

 

Author disclosures
A poster was presented at ESMO (European Society of Medical Oncology) meeting in Singapore, November 22-24, 2019. An abstract was published in Annals of Oncology, 30 (suppl 9), November 2019. The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Background: Radium-223 (Ra-223) radioisotope has been reported to increase median survival in bone metastatic prostate carcinoma. The addition of Ra-223 to abiraterone was associated with an increased risk of bone fractures. There has been no comprehensive data for using Ra-223 in veterans who were exposed to Agent Orange (AO+).

M ethods: We present a retrospective study of veterans with bone metastatic castration-resistant prostate cancer (CRPC) who received standard doses of Ra-223 and other sequential therapies at US Department of Veterans Affairs Pittsburgh Healthcare System in Pennsylvania from 2014 to 2018. Veterans were divided into 2 groups: those who were exposed to Agent Orange (AO+) and those who had no exposure (AO-). Time to study was calculated from the initiation of Ra-223. Time to skeletal-related events (SRE), progression of prostate specific antigen (PSA), bone metastasis, and alkaline phosphatase (ALP) were calculated in months using unpaired t test with 2-tailed P values. Median survival was calculated by Kaplan Meier R log-rank test.

Results: There were 34 veterans with bone metastatic CRPC: 17 veterans (50%) were AO+ and 17 veterans (50%) were AO-. The mean age of diagnosis of AO+ veterans was 62 years and 69 years ( P = .005) for AO- veterans (the mean Gleason score 8.2 and 8.0, respectively [ P = .71]). The median number of Ra-223 cycles was 6 (60%). Ten veterans received Ra-223 as first line (29%) and 24 veterans received Ra-223 later (71%). There were 12 SREs with median survival of 15 months. There was no difference in mean time to SRE between AO+ (8 veterans, 10.6 months) and AO- (4 veterans, 10.3 months) ( P = .93). The mean time to PSA progression for AO+ was 5.4 months and AO- was 6.8 months ( P = .28). Mean time to bone progression for AO+ was 7.6 months and AO- was 10.1 months ( P = .16). Mean time to ALP progression for AO+ and AO- was 6.3 months and 8.7 months, respectively ( P = .05). Twenty veterans (58%) had died. Median survival for Ra-223 first was 32 months and for Ra-223 later was 15 months ( P = .14; hazard ratio [HR] 0.48; 95% CI, 0.17- 1.3). Median survival for AO+ and AO- veterans was 12 months and 18 months, respectively ( P = .15; HR, 2.0; 95% CI, 0.77-5.0).

Conclusions: There was no statistical difference between AO+ and AO- veterans in terms of time to SRE, PSA, bone and ALP progression, even though there was a trend of shorter duration in AO+ veterans. There was no median survival difference between Ra-223 first vs Ra-223 later as well as between AO+ and AO- but there is a trend of worse survival in AO+ veterans.

Conclusions

This is the first VA study to compare the efficacy of Ra-223 and other therapies in metastatic CRPC between AO+ and AO- veterans. AO+ veterans were diagnosed at a younger age and had higher Gleason scores. There was no statistical difference between AO+ and AO- veterans in terms of time to SRE, PSA progression, and bone and ALP progression even though there was a trend of shorter duration in AO+ veterans. There was no median survival difference between veterans who received Ra-223 first vs Ra-223 later as well as between AO+ and AO- veterans, but there was a trend of worse survival in veteran who received Ra-223 later and AO+ veterans.

This study showed that AO+ veterans have a shorter duration of response to therapy and shorter median survival compared with that of AO- veterans. We recommend that veterans should get Ra-223 in the first-line setting rather than after hormonal therapy and chemotherapy because their marrows are still intact. We need to investigate further whether veterans that exposed to carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may have different molecular biology and as such may cause inferior efficacy in the treatment of prostate carcinoma.

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