Clinical Usefulness of Bisphosphonates in Oncology: Treatment of Bone Metastases, antitumoral Activity and Effect on Bone Resorption Markers

2007 ◽  
Vol 22 (1) ◽  
pp. 24-33 ◽  
Author(s):  
A. Verì ◽  
M.R. D'Andrea ◽  
P. Bonginelli ◽  
G. Gasparini
Keyword(s):  
Bone Metastases ◽  
Advanced Disease ◽  
Cord Compression ◽  
Antitumoral Activity ◽  
Pathological Fractures ◽  
Antiangiogenic Activity ◽  
Treatment And Prevention ◽  
Oncology Treatment ◽  
Skeletal Related Events

The present article overviews the role of bisphosphonates for the treatment and prevention of bone metastases and their antiangiogenic effects and antitumoral activity. The skeleton is a frequent and clinically relevant site of metastasis in cancer patients. The major events related to bone metastases include bone pain, bone loss, hypercalcemia, spinal cord compression, and fractures. On the basis of their radiographic features, bone metastases are classified as osteoblastic, osteoclastic, or mixed. The primary goals of treatment of bone metastases are reduction of the risk of pathological fractures and other skeletal-related events, and pain control. Bisphosphonates are used to prevent pathological fractures by inhibition of osteoclasts. Recent studies suggest that bisphosphonates have some direct antitumoral activity, mainly mediated through the blockade of angiogenic pathways. Further clinical studies are needed to determine the optimal treatment duration, timing and schedule of bisphosphonates, assess their role as adjuvant therapy for the prevention of bone metastases, and establish their antiangiogenic activity in association with standard cytotoxic and hormonal drugs for treatment of patients with advanced disease.

scholarly journals Morbidity and mortality of bone metastases in advanced adrenocortical carcinoma: a multicenter retrospective study

2019 ◽  
Vol 180 (5) ◽  
pp. 311-320 ◽  
Author(s):  
Alfredo Berruti ◽  
Rossella Libè ◽  
Marta Laganà ◽  
Hester Ettaieb ◽  
Mohamad Anas Sukkari ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Bone Metastases ◽  
Adrenocortical Carcinoma ◽  
Bone Fractures ◽  
The United States ◽  
Cord Compression ◽  
Risk Of Death ◽  
Skeletal Related Events ◽  
Improve Patient

Introduction Adrenocortical carcinoma (ACC) is a rare cancer that commonly spreads to the liver, lungs and lymph nodes. Bone metastases are infrequent. Objective The aim of this report was to describe the clinical characteristics, survival perspective, prognostic factors and frequency of adverse skeletal-related events (SREs) in patients with ACC who developed bone metastasis. Methods This is a retrospective, observational, multicenter, multinational study of patients diagnosed with bone metastases from ACC who were treated and followed up in three European countries (France, Italy and The Netherlands) and one center in the United States. Results Data of 156 patients were captured. The median overall survival was 11 months. SREs occurred in 47% of patients: 17% bone fractures, 17% spinal cord compression, 1% hypercalcemia, 12% developed more than one SRE. In multivariate analysis, cortisol hypersecretion was the only prognostic factor significantly associated with a higher mortality risk (hazard ratio (HR) 2.24, 95% confidence interval (CI): 1.19–4.23, P = 0.013) and with the development of a SREs (of border line significance). The administration of antiresorptive therapies (bisphosphonates and denosumab) was associated with a lower risk of death, even if not significant, and their survival benefit appeared confined in patients attaining serum mitotane levels within the therapeutic range. Conclusion Bone metastases in ACC patients are associated with poor prognosis and high risk of SREs. Cortisol hypersecretion was the only prognostic factor suggesting a potential benefit from antisecretory medications. The therapeutic role of bisphosphonates and denosumab to improve patient outcome deserves to be tested in a prospective clinical trial.

scholarly journals Dealing with Bone Metastases from Breast Cancer - A Pathological and Clinical Overview

2018 ◽  
Vol 1 (Supplement) ◽  
pp. 25
Author(s):  
O. Munteanu ◽  
A. Dumitru ◽  
O. Bodean ◽  
L. Arsene ◽  
D. Voicu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastases ◽  
Malignant Tumors ◽  
Cord Compression ◽  
Pathological Fractures ◽  
Future Directions ◽  
Skeletal Related Events ◽  
Frequent Site ◽  
Clinical Overview

Abstract From breast malignant tumors, bone is the most frequent site of metastasis. Bone metastases from breast cancer are correlated with pathological fractures, spinal cord compression and other skeletal-related events as well as bone pain and hypercalcemia. These lead to impaired mobility, decreased quality of life, and overall decrease in survival. Clarification of mechanisms regulating bone metastasis has advanced greatly in the last years and this has translated into plentiful unused therapeutic options. Greater understanding of the pathophysiology of bone metastases has led to the detection and clinical efficiency of bone-targeted agents. This review summarizes the key evidence for current clinical practice and future directions.

scholarly journals Practical update for the use of bone-targeted agents in patients with bone metastases from metastatic breast cancer or castration-resistant prostate cancer

2020 ◽  
Vol 27 (4) ◽  
Author(s):  
D. Southcott ◽  
A. Awan ◽  
K. Ghate ◽  
M. Clemons ◽  
R. Fernandes
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Metastatic Breast ◽  
Pathologic Fracture ◽  
Dose Schedule ◽  
Cord Compression ◽  
Targeted Agents ◽  
Castration Resistant Prostate Cancer ◽  
Skeletal Related Events ◽  
Breast And Prostate Cancer

Bone metastases are a significant source of morbidity and mortality for patients with breast and prostate cancer. In this review, we discuss key practical themes regarding the use of bone-targeted agents (btas) such as bisphospho­nates and denosumab for managing bony metastatic disease. The btas both delay the onset and reduce the incidence of skeletal-related events (sres), defined as any or all of a need for radiation therapy or surgery to bone, pathologic fracture, spinal cord compression, or hypercalcemia of malignancy. They have more modest benefits for pain and other quality-of-life measures. Regardless of the benefits of btas, it should always be remembered that the palliative management of meta­static bone disease is multimodal and multidisciplinary. The collaboration of all disciplines is essential for optimal patient care. Special consideration is given to these key questions: What are btas, and what is their efficacy? What are their common toxicities? When should they be initiated? How do we choose the appropriate bta? What is the appropriate dose, schedule, and duration of btas?

Bisphosphonates for Treatment and Prevention of Bone Metastases

2005 ◽  
Vol 23 (32) ◽  
pp. 8219-8224 ◽  
Author(s):  
M. Dror Michaelson ◽  
Matthew R. Smith
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Cord Compression ◽  
Optimal Timing ◽  
Duration Of Treatment ◽  
Treatment And Prevention ◽  
Increased Risk ◽  
Skeletal Complications ◽  
Cancer Complications

Bone metastases are a major cause of morbidity for men with prostate cancer. Complications of bone metastases include pain, fractures, and spinal cord compression. Although they appear osteoblastic by radiographic imaging, most bone metastases are characterized by excess osteoclast number and activity. In addition, pathologic osteoclast activation is associated with increased risk of skeletal complications. Zoledronic acid, a potent inhibitor of osteoclast activity, differentiation, and survival, decreases the risk of skeletal complications in men with androgen-independent prostate cancer and bone metastases. Other bisphosphonates, including pamidronate and clodronate, seem to be ineffective in this setting. The reduction in risk of skeletal complications with zoledronic acid must be weighed against potential adverse effects. Additional studies are needed to determine the optimal timing, schedule, and duration of treatment in men with bone metastases as well as the potential role of bisphosphonates in other settings including the prevention of bone metastases.

Burden of hospitalizations associated with skeletal related events in patients with breast cancer or lung cancer and bone metastases or multiple myeloma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 17083-17083 ◽  
Author(s):  
M. Lage ◽  
D. J. Harrison ◽  
B. Barber ◽  
S. Jun
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Multiple Myeloma ◽  
Bone Metastases ◽  
Index Date ◽  
Opioid Analgesic ◽  
Cord Compression ◽  
Continuous Coverage ◽  
Diagnosis Of Cancer ◽  
Skeletal Related Events

17083 Background: Patients with bone metastases secondary to cancer often experience skeletal related events (SREs) including pathological fracture, spinal cord compression, hypercalcemia, bone surgery or radiotherapy, or initiation of opioid analgesic use. These SREs result in major morbidity and reduced quality of life. This research examines hospitalizations associated with SREs. Methods: Data for this study were obtained from i3 LabRx Database (05/01/2000 to 03/31/2005). Individuals were included in the analyses if they had at least two diagnoses of breast cancer (based upon an ICD-9 code of 174.xx), lung cancer (162.xx), or multiple myeloma (203.0x) and had at least two diagnoses of bone metastases (198.5x) after the first diagnosis of cancer. In addition, individuals were required to have at least one SRE (based upon a previously published algorithm) on or after their initial diagnosis of bone metastases (their index date). Individuals were required to be continuously insured for at least 6 months prior to, and at least one month post their index date. Data were analyzed until 03/31/2005 or until the end of their continuous coverage, whichever occurred first. Descriptive statistics for each of these cohorts are provided. Results: A total of 1,204 individuals with breast cancer, 1,094 with lung cancer, and 258 with multiple myeloma were included in the study. The vast majority of individuals with breast cancer (96.5%), lung cancer (95.9%), or multiple myeloma (96.8%) were hospitalized. All three patient groups were likely to have SRE-related hospitalizations; multiple myeloma 43.4%, breast cancer 36.2% and lung cancer 35.6%. The average number of days per patient year that patients were hospitalized related to a diagnosis or procedure for a SRE was 6.75 days for patients with lung cancer, 6.56 days for patients with multiple myeloma, and 3.75 days for patients with breast cancer. Conclusion: Hospitalizations related to SREs are common and the number of days per year is substantial. No significant financial relationships to disclose.

Skeletal related events in patients with metastatic renal cell carcinoma: A retrospective review

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16118-e16118
Author(s):  
M. Secter ◽  
M. J. MacKenzie ◽  
P. O'Brien ◽  
F. Whiston
Keyword(s):  
Renal Cell Carcinoma ◽  
Bone Metastases ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Retrospective Review ◽  
Renal Cell ◽  
Length Of Hospital Stay ◽  
Pathologic Fracture ◽  
Cord Compression ◽  
Skeletal Related Events

e16118 Background: Approximately one third of patients with renal cell carcinoma (RCC) will develop bone metastases during the course of their disease. Previous studies suggest that the rate of skeletal related events (SREs) in patients with metastatic renal cell carcinoma is high, and that bisphosphonate therapy can lower the rate of SREs. We conducted a retrospective review of patients with metastatic renal cell carcinoma and bone metastases seen at our academic cancer centre. Methods: After approval by the Research Ethics Board, a retrospective review of all patients seen at the London Regional Cancer Centre with a diagnosis of RCC between January 2006 and December 2008 was performed. Data points collected included the number of patients with bone metastases, number of SREs, length of hospital stay, and treatments related to SREs. A SRE was defined as one of the following: pathologic fracture, spinal cord compression, radiotherapy or surgery to bone, or hypercalcemia in the presence of bone metastases. Results: 196 patients with metastatic RCC were identified. Of these, 63 (32%) had bone metastases. 75% of these patients with bone metastases received medical therapies including sunitinib, sorafenib or temsirolimus. 66% of patients received at least one dose of bisphosponate therapy. Common sites of metastases were vertebra (66%), pelvis (50%), and femur (42%). Of those with bone metastases, 61 (95%) experienced at least one SRE. 42% sustained a pathologic fracture; 28% suffered a spinal cord compression or cauda equina syndrome; 22% had surgery for bone metastases; 87.5% required radiotherapy and 27% had hypercalcemia. 40% of patients were hospitalized due to an SRE, and the mean length of hospital stay was 21 days (range 1–120 days). Conclusions: Despite significant recent improvements in the overall care of RCC, and expansion of the number of therapeutic options, bone metastases and consequent SREs continue to cause significant morbidity. These SREs come with frequent and prolonged hospitalizations. Our rate of SREs is actually higher than that documented in the placebo arm of a randomized trial of a bisphosphonate in RCC from the pre-tyrosine kinase era. Bone-related morbidity in mRCC remains a clinical problem with a significant unmet medical need. [Table: see text]

scholarly journals Denosumab: A comprehensive review

2013 ◽  
Vol 02 (04) ◽  
pp. 272-277 ◽  
Author(s):  
Prasad Narayanan
Keyword(s):  
Bone Resorption ◽  
Bone Metastases ◽  
Human Monoclonal Antibody ◽  
Bone Destruction ◽  
Clinical Trial Data ◽  
Osteoclast Formation ◽  
Future Challenges ◽  
Formation Function ◽  
Skeletal Related Events

AbstractThe clinical sequelae from bone metastases, termed skeletal-related events (SREs), are among the most frequent and debilitating complications in patients with advanced cancer. Bone metastases are characterized by pathologically increased osteoclast activity, and accumulating evidence indicates that tumor cells interact within the bone to stimulate the receptor activator of nuclear factor kB (RANK)-RANK ligand (RANKL) pathway. RANKL is an essential mediator of osteoclast formation, function, and survival. Because of the central role of RANKL in cancer-induced bone destruction, the inhibition of RANKL has the potential to result in the reduction of pathologic bone resorption. Denosumab is a fully human monoclonal antibody specific for RANKL that inhibits the formation, activation, and survival of osteoclasts. This in turn decreases bone resorption and reduces cancer-induced bone destruction. In this review, we give an overview of the drug Denosumab with its history, mechanism of action, clinical trial data, adverse effects, and future challenges.

Direct hospital costs of skeletal-related events (SRE) in Portuguese patients (pts) with breast cancer (BC) and bone metastases

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 17084-17084 ◽  
Author(s):  
J. Felix ◽  
V. Andreozzi ◽  
M. Soares ◽  
H. Gervásio ◽  
A. Moreira ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Radiation Therapy ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Treatment Cost ◽  
Hospital Costs ◽  
Cord Compression ◽  
Health Resource ◽  
Health Resource Utilization ◽  
Pathological Fractures

17084 Background: SRE such as pathological fractures, spinal cord compression, surgery or radiation therapy to bone and tumour- induced hypercalcemia account for substantial health resource utilization (HRU). The objective of this study was to investigate SRE-related direct hospital costs in Portuguese pts with BC and bone metastases. Methods: Pts with BC and at least one SRE within 12 months prior to study entry were eligible for this retrospective medical record review cost analysis study. SRE treatment cost were calculated by multiplying 12 month health resource utilization frequency (hospitalization, clinic visits, diagnostic tests, drugs) by the corresponding unit costs from the Portuguese Ministry of Health costs database. To account for the skewed nature of the data, costs were modelled using generalized linear models with gamma distribution and log link. Results: A total of 121 pts (age at bone metastases, mean 56.8 years, range 21- 89) from six different hospitals in Portugal were included. Median time from BC diagnosis to bone metastases was 38 months [CI95%: 24–57]. ECOG performance status at the time of SRE was 0 in 24.6% of pts, 1 in 45.9%, 2 in 18.0%, 3 in 8.2% and 4 in 3.3%. Total number of SRE over twelve months was 142 (mean 1.2 SRE/pts, SD=0.4) distributed as follows: pathological fractures (12.7%), spinal cord compression (4.9%), surgery to bone (1.4%), radiation therapy to bone (74.7%) and tumour induced hypercalcemia (6.3%) . Mean SRE treatment cost over 12 months was 5,963€ (SD=3,646€): hospitalization 1,312€, clinic visits 36€, diagnostics 103€, radiotherapy 1,481€, drugs 3,031€. According to biphosphonate (Bph) use in the prior 12 months, the mean (SD; pts) unadjusted SRE treatment cost was: no Bph 2,282€ (1,491; n=4), oral Bph 1,579€ (1,123; n=5), zoledronic acid 6,221€ (2,923; n=77), pamidronate 6,766€ (4,476; n=33). When excluding Bph costs, pamidronate pts were 1.8 [95% CI: 1.3–2.7] times more expensive than zoledronic acid when controlling for pts’ clinical characteristics. Conclusions: This study confirms prior data on the high cost of SRE in pts with BC metastatic to bone [Table: see text]

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