Burden of skeletal-related events in prostate cancer: unmet need in pain improvement

Broder, Michael S.; Gutiérrez, Benjamín; Cherepanov, Dasha; Linhares, Yuliya

doi:10.1007/s00520-014-2437-3

Cited by 50 publications

(42 citation statements)

References 44 publications

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“…This leads to increased risk of skeletal fractures, immobility, severe bone pain, a significant decrease in quality of life, increased mortality and, consequently, remarkable economic burden (3, 4). Therefore, the elimination of cancer in bone and the restoration and/or preservation of healthy bone morphology are important goals in the management and treatment of prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Radium-223 Inhibits Osseous Prostate Cancer Growth by Dual Targeting of Cancer Cells and Bone Microenvironment in Mouse Models

Suominen

Fagerlund

Rissanen

et al. 2017

Clinical Cancer Research

142

118

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Purpose Radium-223 dichloride (radium-223, Xofigo®), a targeted alpha therapy, is currently used for the treatment of patients with castration-resistant prostate cancer (CRPC) with bone metastases. This study examines the mode-of-action and antitumor efficacy of radium-223 in two prostate cancer xenograft models. Experimental Design Mice bearing intratibial LNCaP or LuCaP 58 tumors were randomized to groups (n = 12–17) based on lesion grade and/or serum PSA level and administered with radium-223 (300 kBq/kg) or vehicle, twice at 4-week intervals. X-rays and serum samples were obtained biweekly. Soft tissue tumors were observed macroscopically at sacrifice. Tibiae were analyzed by gamma counter, micro-CT, autoradiography and histology. Results Radium-223 inhibited tumor-induced osteoblastic bone growth and protected normal bone architecture leading to reduced bone volume in LNCaP and abiraterone-resistant LuCaP 58 models. Furthermore, radium-223 resulted in lower PSA values and reduced total tissue and tumor areas, indicating that treatment constrains prostate cancer growth in bone. In addition, radium-223 suppressed abnormal bone metabolic activity as evidenced by decreased number of osteoblasts and osteoclasts and reduced level of the bone formation marker PINP. Mode-of-action studies revealed that radium-223 was deposited in the intratumoral bone matrix. DNA double-strand breaks were induced in cancer cells within 24 hours after radium-223 treatment and PSA levels were significantly lower 72 hours post treatment providing further evidence of the anti-tumor effects. Conclusion Taken together, radium-223 therapy exhibits a dual targeting mode-of-action that induces tumor cell death and suppresses tumor-induced pathological bone formation in tumor microenvironment in osseous CRPC growth in mice.

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Section: Introductionmentioning

confidence: 99%

Radium-223 Inhibits Osseous Prostate Cancer Growth by Dual Targeting of Cancer Cells and Bone Microenvironment in Mouse Models

Suominen

Fagerlund

Rissanen

et al. 2017

Clinical Cancer Research

142

118

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“…Skeletal-related events (SREs) are a major cause of morbidity and mortality in patient's metastatic castration-resistant prostate cancer [15,16] (mCRPC). In the trial COU-AA-301, occurrence of new SREs was 29% with AA and 33% with placebo; time to first SRE was significantly longer with AA [10,11] (median 25.0 vs. 20.3 months HR 0.615; p=0.0001).…”

Section: Role Of Abiraterone In Skeletal Metastasis In Patients With mentioning

confidence: 99%

Abiraterone: A Review of its Pharmacokinetic, Pharmacodynamic Profile and Clinical Efficacy

Mehta¹,

Barkate²

2016

UNOAJ

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Prostate cancer is a common cancer and it causes significant morbidity and mortality in elderly males. Management for metastatic castration resistant prostate cancer has improved tremendously over the last decade with newer agents improving overall survival and quality of life of patients. Until recently, docetaxel was the only agent to show an improvement in overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). Of late, many new agents with different mode of action and therapeutic targets have improved overall survival and several new drugs (Cabazitaxel, Sipuleucel-T, abiraterone acetate, Enzalutamide and radium -233) were FDA approved for the treatment of patients with mCRPC. This article reviews current concepts and emerging treatment options in mCRPC followed by phase III studies of abiraterone and newer emerging role of abiraterone like the effect of low dose abiraterone acetate with food and the role of abiraterone as neoadjuvant therapy for localized high risk prostate cancer (LHRPC). The review will also discuss the role of abiraterone in skeletal related events as they are a major cause of morbidity and mortality in patients with metastatic castration-resistant prostate cancer.

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“…Bone metastases are commonly associated with bone complications, known as skeletal-related events (SREs), including pathologic fracture, spinal cord compression and radiation or surgery to bone. SREs cause severe pain, reduced mobility, functional dependency, increased demand for analgesics and result in a reduced overall health-related quality of life [5–8]. …”

Section: Introductionmentioning

confidence: 99%

An observational time and motion study of denosumab subcutaneous injection and zoledronic acid intravenous infusion in patients with metastatic bone disease: results from three European countries

Body

Gatta

Cock³

et al. 2017

Support Care Cancer

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PurposeDenosumab (administered via subcutaneous injection) demonstrated superior efficacy versus the intravenously administered zoledronic acid in the prevention of skeletal-related events in an integrated analysis of three head-to-head phase III trials in patients with bone metastases secondary to solid tumors. To date, no studies have evaluated treatment administration duration endpoints of these two agents.MethodsA multinational, multi-site, observational time and motion study conducted in 10 day oncology units (DOUs) across Belgium, Germany, and Italy. Observations of process time included task time and active healthcare professional (HCP) time for pre-defined tasks. Patient time measurements included entering/exiting the DOU, treatment room, and treatment chair or examination table.ResultsA total of 189 patients were enrolled (82 received zoledronic acid and 107 received denosumab) and 238 observations were recorded (104 for zoledronic acid and 134 for denosumab). Mean total task time was reduced by 81% when denosumab was used versus zoledronic acid (8.4 versus 44.2 min; p < 0.0001; pooled analysis across all countries). Pooled estimates for active HCP time were 12.2 min for zoledronic acid and 6.9 min for denosumab (44% reduction; p < 0.0001).ConclusionsIn the countries studied, using denosumab compared with zoledronic acid reduced total task time and active HCP time. Thus, HCPs have more time to dedicate to other patients or care activities. An ability to increase the volume of appointments within DOUs could reduce waiting lists in sites operating at full capacity and increase overall productivity and efficiency in hospital processes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00520-017-3697-5) contains supplementary material, which is available to authorized users.

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Burden of skeletal-related events in prostate cancer: unmet need in pain improvement

Abstract: Specific SREs are associated with worse outcomes, including increased pain, poorer QOL, morbidity, and survival. Treatment of SREs is associated with improved pain, although there remains a need for more effective treatment of SREs in prostate cancer patients.

Cited by 50 publications

References 44 publications

Radium-223 Inhibits Osseous Prostate Cancer Growth by Dual Targeting of Cancer Cells and Bone Microenvironment in Mouse Models

Radium-223 Inhibits Osseous Prostate Cancer Growth by Dual Targeting of Cancer Cells and Bone Microenvironment in Mouse Models

Abiraterone: A Review of its Pharmacokinetic, Pharmacodynamic Profile and Clinical Efficacy

An observational time and motion study of denosumab subcutaneous injection and zoledronic acid intravenous infusion in patients with metastatic bone disease: results from three European countries

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