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Bone targeted therapies for the prevention of skeletal morbidity in men with prostate cancer.

Men with prostate cancer suffer substantially from bone-related complications. Androgen deprivation therapy itself is a cause of loss of bone mineral density and is associated with an increased incidence of osteoporotic fractures. In advanced disease, bone is by far the most common site of metastasis. Complications of bone metastases prominently include pain and the potential for skeletal events such as spinal cord compression and pathologic fractures. Elevated osteoclast activity is an important aspect of the pathophysiology of both treatment-related osteoporosis and skeletal complications du

MASCC/ISOO Clinical Practice Statement: Adjuvant bone-modifying agents in primary breast cancer patients - prevention of medication-related osteonecrosis of the jaw.

PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS raises awareness to the prevention of medication-related osteonecrosis of the jaw (MRONJ) in patients with breast cancer treated with adjuvant bone-modifying agents (BMA). METHODS: This CPS was developed based on a critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. T

The incidence and relative risk of adverse events in patients treated with bisphosphonate therapy for breast cancer: a systematic review and meta-analysis.

BACKGROUND: Adjuvant bisphosphonates reduce the rate of breast cancer recurrence in the bone and improve breast cancer survival. However, the risk of adverse events associated with bisphosphonate therapy for breast cancer remains poorly defined. METHODS: A literature search was conducted using the PubMed, EMBASE, Cochrane and Web of Science libraries. Risk ratio (RR) was calculated to evaluate the adverse events of the meta-analytic results. Osteonecrosis of the jaw (ONJ) incidence was calculated using the random effect model (D+L pooled) for meta-analysis. RESULTS: A total of 47 studies com

Use of bisphosphonates in prostate cancer: Current status.

Bisphosphonates are a relatively newer class of drugs which have been used for the prevention of skeletal related complications of age related osteoporosis or metastatic disease from carcinoma breast or multiple myeloma. Their role in the management of prostate cancer is still under evolution. We hereby review the ongoing and some published randomized trials to define the role of bisphosphonates in various stages of prostate cancer.

The Effect of Bisphosphonates on Fracture Healing Time and Changes in Bone Mass Density: A Meta-Analysis.

BackgroundOsteoporosis is a common complication of acute fracture, which can lead to fracture delayed union or other complications and resulting in poor fracture healing. Bisphosphate is a common anti-osteoporosis drug, but its application in fracture patients is still controversial because of its inhibitory effect on bone resorption.MethodStudies were acquired from literature databases in accordance with established inclusion criteria. Standard mean difference (SMD) and 95% confidence intervals (Cls) were calculated to evaluate the effectiveness of the bisphosphonates treatment in fracture pa

Skeletal morbidity rates over time in patients with bone metastases from solid tumors reported in bone modifying agents randomised trials.

ObjectiveSkeletal related events (SREs) are common in patients with bone metastases and lead to decreased quality of life and functional status. The definition of an SRE has evolved over the years and now excludes hypercalcemia of malignancy due to its low incidence. The purpose of this review was to investigate if advances in bone-targeted therapies have decreased skeletal morbidity rates (SMR) over time.MethodsA literature search was conducted in several databases to identify phase III results from bone-targeted therapy trials from 1980 through September 2011. Graphs were created to document

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… medical subject headings and text words were used: “exp neoplasms”, “cancer”, “carcinoma”, “tumor”, “malignan:”, “bone neoplasms/sc” (secondary), “bone metast:”, “osseous metast:”, “bone pain”, combined with “exp diphosphonates”, “bisphosphonate”, “exp alendronate”, “alendronate”, “alendronic acid”, “exp clodronic … acid”, “clodronic acid”, “clodronate”, “dichloromethylene”, “exp etidronic acid”, “etidronic acid”, “etidronate”, “exp ibandronate”, “ibandronate”, “ibandronic acid”, “pamidronate”, “aredia”, “exp zoledronic acid”, “zoledronic acid”, “zolendronate”, “zometa”, and “denosumab”. …

Bone-targeted therapies in metastatic castration-resistant prostate cancer: evolving paradigms.

Majority of patients with metastatic castrate resistant prostate cancer (mCRPC) develop bone metastases which results in significant morbidity and mortality as a result of skeletal-related events (SREs). Several bone-targeted agents are either in clinical use or in development for prevention of SREs. Bisphosphonates were the first class of drugs investigated for prevention of SREs and zoledronic acid is the only bisphosphonate that is FDA-approved for this indication. Another bone-targeted agent is denosumab which is a fully humanized monoclonal antibody that binds to the RANK-L thereby inhibi

Multiple Myeloma and the Role of Bisphosphonates in Its Management.

An aberrant growth of plasma cells in the bone marrow characterizes the hematological neoplasm known as multiple myeloma, which is typically accompanied by increased bone pain and skeletal-related events such as pathological fractures and/or spinal cord compression. Changes in the bone marrow microenvironment brought on by increased osteoclastic activity and/or decreased osteoblastic activity as a result of myeloma bone disease have a detrimental effect on quality of life. Bone-modifying medications such as bisphosphonates or denosumab are used to treat myeloma bone disease. These substances c

Improving management of patients with advanced cancer.

Development of bone metastases in patients with advanced cancer is associated with skeletal-related events (SREs) such as pathologic fractures, spinal cord compression, the requirement for surgery or palliative radiotherapy to bone, and hypercalcemia of malignancy. Skeletal morbidity may reduce patient mobility, limit functional independence, and impair quality of life (QOL). Proactive management of new or worsening bone pain or motor impairment is crucial because of the potential for rapid progression of symptoms. Administration of bisphosphonate therapy as a monthly infusion to patients with

Targeting Bone Metastases in Metastatic Castration-Resistant Prostate Cancer.

Skeletal involvement in metastatic castrate-resistant prostate cancer (mCRPC) is common and results in significant morbidity and mortality. The interaction of prostate cancer with the bone microenvironment contributes to progression of cancer in the bone leading to skeletal-related events (SREs). Studies aimed at targeting the bone have been carried out over the recent years. Bisphosphonates are synthetic pyrophosphate analogs first investigated for their role in SRE prevention with zoledronic acid as the main bisphosphonate that is approved by the US Food and Drug Administration for retardati

Where Do Bone-Targeted Agents RANK in Breast Cancer Treatment?

Breast cancer cells preferentially metastasise to the skeleton, owing, in part, to the fertile environment provided by bone. Increased bone turnover releases growth factors that promote tumour cell growth. In turn, tumour cells release factors that stimulate further bone turnover, resulting in a vicious cycle of metastasis growth and bone destruction. The RANK-RANK ligand (RANKL) pathway plays a key role in this cycle, and inhibition of RANKL using the fully-human monoclonal antibody denosumab, has demonstrated efficacy in delaying skeletal complications associated with bone metastases in thre

Diagnosis and treatment of bone metastasis: comprehensive guideline of the Japanese Society of Medical Oncology, Japanese Orthopedic Association, Japanese Urological Association, and Japanese Society for Radiation Oncology.

Diagnosis and treatment of bone metastasis requires various types of measures, specialists and caregivers. To provide better diagnosis and treatment, a multidisciplinary team approach is required. The members of this multidisciplinary team include doctors of primary cancers, radiologists, pathologists, orthopaedists, radiotherapists, clinical oncologists, palliative caregivers, rehabilitation doctors, dentists, nurses, pharmacists, physical therapists, occupational therapists, medical social workers, etc. Medical evidence was extracted from published articles describing meta-analyses or random

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… First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet 2010;376:1989–99. 10.1016/S0140-6736(10)62051-X 73. Morgan GJ, Child JA, Gregory WM et al. … Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): secondary outcomes from a randomised controlled trial. Lancet Oncol 2011;12:743–52. 10.1016/S1470-2045(11)70157-7 74. …

Protection of bone in premenopausal women with breast cancer: focus on zoledronic acid.

Maintaining bone health is important for patients with breast cancer (BC), the most commonly diagnosed cancer in American women. Indeed, bone loss is common throughout the BC disease continuum. In the metastatic BC setting, patients are likely to develop bone metastases, a painful complication that can lead to potentially debilitating skeletal-related events. Bone health is equally important for patients with early BC. During adjuvant therapy for early BC, the largest challenge to bone health is from accelerated bone mineral density (BMD) loss. Although decreased BMD is well recognized in olde

Anti-tumour activity of bisphosphonates in preclinical models of breast cancer.

There is increasing evidence of anti-tumour effects of bisphosphonates from pre-clinical studies, supporting a role for these drugs beyond their traditional use in treatment of cancer-induced bone disease. A range of model systems have been used to investigate the effects of different bisphosphonates on tumour growth, both in bone and at peripheral sites. Most of these studies conclude that bisphosphonates cause a reduction in tumour burden, but that early intervention and the use of high and/or repeated dosing is required. Successful eradication of cancer may only be achievable by targeting t

Bisphosphonates in oncology: evidence for the prevention of skeletal events in patients with bone metastases.

Bone metastases frequently occur in patients with advanced solid tumors, particularly breast and prostate cancers, and nearly all patients with multiple myeloma have some degree of skeletal involvement. The strides made in treating these primary tumors have extended median survival times and thereby increased patient risk for skeletal-related events (SREs), including pathologic fractures, spinal cord compression, need for palliative radiation therapy or surgery to bone, and hypercalcemia. Bisphosphonates, inhibitors of osteoclastic bone resorption that were first established as treatment of os

Bone targeted treatments in cancer - The story so far.

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… First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomized controlled trial. Lancet. 2010;376:1989–1999. doi: 10.1016/S0140-6736(10)62051-X. 18. Lacey D.L., Boyle W.J., Simonet W.S. …

New agents in the Treatment of Myeloma Bone Disease.

Patients with multiple myeloma develop a devastating bone disease driven by the uncoupling of bone remodelling, excess osteoclastic bone resorption and diminished osteoblastic bone formation. The bone phenotype is typified by focal osteolytic lesions leading to pathological fractures, hypercalcaemia and other catastrophic bone events such as spinal cord compression. This causes bone pain, impaired functional status, decreased quality of life and increased mortality. Early in the disease, malignant plasma cells occupy a niche environment that encompasses their interaction with other key cellula

Multiple Myeloma Associated Bone Disease.

The lytic bone disease is a hallmark of multiple myeloma, being present in about 80% of patients with newly diagnosed MM, and in more during the disease course. The myeloma associated bone disease (MBD) severely affects the morbidity and quality of life of the patients. MBD defines treatment demanding MM. In recent years, knowledge of the underlying pathophysiology has increased, and novel imaging technologies, medical and non-pharmaceutical treatments have improved. In this review, we highlight the major achievements in understanding, diagnosing and treating MBD. For diagnosing MBD, low-dose

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… First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): A randomised controlled trial Lancet 2010 376 1989 1999 10.1016/S0140-6736(10)62051-X 21131037 PMC3639680 69. Morgan G.J. Child J.A. Gregory W.M. Szubert A.J. Cocks K. Bell S.E. … Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): Secondary outcomes from a randomised controlled trial Lancet Oncol. 2011 12 743 752 10.1016/S1470-2045(11)70157-7 21771568 PMC3148431 70. Mhaskar R. Kumar A. …

Indian Society for Study of Pain, Cancer Pain Special Interest Group Guidelines on Pharmacological Management of Cancer Pain (Part III).

The Indian Society for Study of Pain (ISSP), Cancer Pain Special Interest Group, guidelines on pharmacological management of cancer pain in adults provide a structured, step-wise approach which will help to improve the management of cancer pain and to provide patients with a minimally acceptable quality of life. The guidelines have been developed based on the available literature and evidence, to suit the needs, patient population, and situations in India. A questionnaire based on the key elements of each sub draft addressing certain inconclusive areas where evidence was lacking, was made avai

Лечение болезни костей миэломы: Когда, как часто и как долго?

Площадь ММ в последние годы резко изменилась. Было введено несколько новых и более эффективных методов лечения, которые не только делают пациентов более продолжительными, но и приводят их к более глубокой ремиссии. Это делает потенциальное общее воздействие защитной обработки костей гораздо более высоким, но, возможно, и менее необходимым. Введены новые и более точные методы воображения, которые делают обнаружение костных заболеваний более чувствительным, и введение критериев SLIM-CRAB изменило параметры, использовавшиеся в старых клинических испытаниях для исследования лечения костных заболев

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… /First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX) : a randomised controlled trial. … First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010;376(9757):744–751. doi: 10.1016/S0140-6736(10)62051-X. 85. …