Impact of timing of administration of bone supportive therapy on pain palliation from radium-223

Kelly Khai Li Yap, William Wong, Lingyun Ji, Susan Groshen, David I. Quinn, Alan H Bryce, Tanya B. Dorff

Research output: Contribution to journalArticle

Abstract

Background: Skeletal-related events cause significant morbidity in patients with metastatic castration-resistant prostate cancer. In the ALSYMPCA study, radium-223 (Ra223) was found to provide pain palliation in addition to prolonged survival and reduced skeletal-related events (SREs). Given previous evidence that bisphosphonates impacted pain relief from the radiopharmaceutical samarium-153, we evaluated whether the timing of bone supportive therapy (BST) such as zoledronic acid or denosumab affected pain palliation from Ra223. Methods: We identified patients who received Ra223 at University of Southern California or Mayo Clinic Arizona. Patients were evaluable for pain response if they had baseline pain score > 0 and at least 1 pain score documented after Ra223 with pain medication use data. Patients were evaluable for pain flare if they had known baseline pain score and at least 2 pain scores documented after Ra223. Pain response was defined as > 2 point decrease in pain on a 10-point scale; flare was defined as > 2 point increase followed by return to baseline or lower. Results: Of 65 patients, 22 (34%) received BST. Median number of doses Ra223 was 5 (range 2–6). Fourteen patients were evaluable for pain response and 34 for pain flare. Eighteen patients received concurrent abiraterone (abi) or enzalutamide (enza), and 16 did not. Pain response occurred in 6/6 (100%) patients who received BST within 1 month prior to first Ra223 dose and 4/8 (50%) patients who did not receive BST. Pain flare occurred in 6/21 patients (29%) without BST and 2/13 (15%) with BST (p = 0.44). 6/10 (60%) patients with pain response had a decline in alkaline phosphatase (ALP) level, but there was no consistent pattern of ALP changes in patients with flare. 8/8 patients with pain response had no PSA decline. 6/8 (75%) and 2/18 (11%) patients on abi/enza had pain response and flare respectively, and 4/6 (67%) and 6/16 (38%) patients without concurrent abi/enza had response/flare. Conclusions: BST within 1 month prior to first Ra223 dose was associated with increased likelihood of pain palliation and might prevent pain flare. Concurrent use of abi/enza was not associated with increased likelihood of pain response but was associated with decreased likelihood of pain flare.

Original languageEnglish (US)
Article number100114
JournalCancer Treatment and Research Communications
Volume18
DOIs
StatePublished - Jan 1 2019

Fingerprint

Radium
Bone and Bones
Pain
Therapeutics
zoledronic acid
Alkaline Phosphatase

Keywords

  • Bisphosphonate
  • Denosumab
  • mCRPC
  • Pain flare
  • Pain response
  • Prostate cancer
  • Radium223
  • Rank ligand

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Impact of timing of administration of bone supportive therapy on pain palliation from radium-223. / Yap, Kelly Khai Li; Wong, William; Ji, Lingyun; Groshen, Susan; Quinn, David I.; Bryce, Alan H; Dorff, Tanya B.

In: Cancer Treatment and Research Communications, Vol. 18, 100114, 01.01.2019.

Research output: Contribution to journalArticle

Yap, Kelly Khai Li ; Wong, William ; Ji, Lingyun ; Groshen, Susan ; Quinn, David I. ; Bryce, Alan H ; Dorff, Tanya B. / Impact of timing of administration of bone supportive therapy on pain palliation from radium-223. In: Cancer Treatment and Research Communications. 2019 ; Vol. 18.
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abstract = "Background: Skeletal-related events cause significant morbidity in patients with metastatic castration-resistant prostate cancer. In the ALSYMPCA study, radium-223 (Ra223) was found to provide pain palliation in addition to prolonged survival and reduced skeletal-related events (SREs). Given previous evidence that bisphosphonates impacted pain relief from the radiopharmaceutical samarium-153, we evaluated whether the timing of bone supportive therapy (BST) such as zoledronic acid or denosumab affected pain palliation from Ra223. Methods: We identified patients who received Ra223 at University of Southern California or Mayo Clinic Arizona. Patients were evaluable for pain response if they had baseline pain score > 0 and at least 1 pain score documented after Ra223 with pain medication use data. Patients were evaluable for pain flare if they had known baseline pain score and at least 2 pain scores documented after Ra223. Pain response was defined as > 2 point decrease in pain on a 10-point scale; flare was defined as > 2 point increase followed by return to baseline or lower. Results: Of 65 patients, 22 (34{\%}) received BST. Median number of doses Ra223 was 5 (range 2–6). Fourteen patients were evaluable for pain response and 34 for pain flare. Eighteen patients received concurrent abiraterone (abi) or enzalutamide (enza), and 16 did not. Pain response occurred in 6/6 (100{\%}) patients who received BST within 1 month prior to first Ra223 dose and 4/8 (50{\%}) patients who did not receive BST. Pain flare occurred in 6/21 patients (29{\%}) without BST and 2/13 (15{\%}) with BST (p = 0.44). 6/10 (60{\%}) patients with pain response had a decline in alkaline phosphatase (ALP) level, but there was no consistent pattern of ALP changes in patients with flare. 8/8 patients with pain response had no PSA decline. 6/8 (75{\%}) and 2/18 (11{\%}) patients on abi/enza had pain response and flare respectively, and 4/6 (67{\%}) and 6/16 (38{\%}) patients without concurrent abi/enza had response/flare. Conclusions: BST within 1 month prior to first Ra223 dose was associated with increased likelihood of pain palliation and might prevent pain flare. Concurrent use of abi/enza was not associated with increased likelihood of pain response but was associated with decreased likelihood of pain flare.",
keywords = "Bisphosphonate, Denosumab, mCRPC, Pain flare, Pain response, Prostate cancer, Radium223, Rank ligand",
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T1 - Impact of timing of administration of bone supportive therapy on pain palliation from radium-223

AU - Yap, Kelly Khai Li

AU - Wong, William

AU - Ji, Lingyun

AU - Groshen, Susan

AU - Quinn, David I.

AU - Bryce, Alan H

AU - Dorff, Tanya B.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Skeletal-related events cause significant morbidity in patients with metastatic castration-resistant prostate cancer. In the ALSYMPCA study, radium-223 (Ra223) was found to provide pain palliation in addition to prolonged survival and reduced skeletal-related events (SREs). Given previous evidence that bisphosphonates impacted pain relief from the radiopharmaceutical samarium-153, we evaluated whether the timing of bone supportive therapy (BST) such as zoledronic acid or denosumab affected pain palliation from Ra223. Methods: We identified patients who received Ra223 at University of Southern California or Mayo Clinic Arizona. Patients were evaluable for pain response if they had baseline pain score > 0 and at least 1 pain score documented after Ra223 with pain medication use data. Patients were evaluable for pain flare if they had known baseline pain score and at least 2 pain scores documented after Ra223. Pain response was defined as > 2 point decrease in pain on a 10-point scale; flare was defined as > 2 point increase followed by return to baseline or lower. Results: Of 65 patients, 22 (34%) received BST. Median number of doses Ra223 was 5 (range 2–6). Fourteen patients were evaluable for pain response and 34 for pain flare. Eighteen patients received concurrent abiraterone (abi) or enzalutamide (enza), and 16 did not. Pain response occurred in 6/6 (100%) patients who received BST within 1 month prior to first Ra223 dose and 4/8 (50%) patients who did not receive BST. Pain flare occurred in 6/21 patients (29%) without BST and 2/13 (15%) with BST (p = 0.44). 6/10 (60%) patients with pain response had a decline in alkaline phosphatase (ALP) level, but there was no consistent pattern of ALP changes in patients with flare. 8/8 patients with pain response had no PSA decline. 6/8 (75%) and 2/18 (11%) patients on abi/enza had pain response and flare respectively, and 4/6 (67%) and 6/16 (38%) patients without concurrent abi/enza had response/flare. Conclusions: BST within 1 month prior to first Ra223 dose was associated with increased likelihood of pain palliation and might prevent pain flare. Concurrent use of abi/enza was not associated with increased likelihood of pain response but was associated with decreased likelihood of pain flare.

AB - Background: Skeletal-related events cause significant morbidity in patients with metastatic castration-resistant prostate cancer. In the ALSYMPCA study, radium-223 (Ra223) was found to provide pain palliation in addition to prolonged survival and reduced skeletal-related events (SREs). Given previous evidence that bisphosphonates impacted pain relief from the radiopharmaceutical samarium-153, we evaluated whether the timing of bone supportive therapy (BST) such as zoledronic acid or denosumab affected pain palliation from Ra223. Methods: We identified patients who received Ra223 at University of Southern California or Mayo Clinic Arizona. Patients were evaluable for pain response if they had baseline pain score > 0 and at least 1 pain score documented after Ra223 with pain medication use data. Patients were evaluable for pain flare if they had known baseline pain score and at least 2 pain scores documented after Ra223. Pain response was defined as > 2 point decrease in pain on a 10-point scale; flare was defined as > 2 point increase followed by return to baseline or lower. Results: Of 65 patients, 22 (34%) received BST. Median number of doses Ra223 was 5 (range 2–6). Fourteen patients were evaluable for pain response and 34 for pain flare. Eighteen patients received concurrent abiraterone (abi) or enzalutamide (enza), and 16 did not. Pain response occurred in 6/6 (100%) patients who received BST within 1 month prior to first Ra223 dose and 4/8 (50%) patients who did not receive BST. Pain flare occurred in 6/21 patients (29%) without BST and 2/13 (15%) with BST (p = 0.44). 6/10 (60%) patients with pain response had a decline in alkaline phosphatase (ALP) level, but there was no consistent pattern of ALP changes in patients with flare. 8/8 patients with pain response had no PSA decline. 6/8 (75%) and 2/18 (11%) patients on abi/enza had pain response and flare respectively, and 4/6 (67%) and 6/16 (38%) patients without concurrent abi/enza had response/flare. Conclusions: BST within 1 month prior to first Ra223 dose was associated with increased likelihood of pain palliation and might prevent pain flare. Concurrent use of abi/enza was not associated with increased likelihood of pain response but was associated with decreased likelihood of pain flare.

KW - Bisphosphonate

KW - Denosumab

KW - mCRPC

KW - Pain flare

KW - Pain response

KW - Prostate cancer

KW - Radium223

KW - Rank ligand

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