Clinical Oncology

[Bone metastases - Current treatment strategy]

BOÉR Katalin, NÉMETH Zsuzsanna

DECEMBER 05, 2014

Clinical Oncology - 2014;1(04)

[Bone is the most common site of metastatic disease in many solid tumours, mainly in breast, prostate and lung cancer. Patients with bone metastases are at risk for skeletal-related events such as bone pain, pathological fractures requiring surgery and/or radiation to bone lesions, hypercalcemia, and spinal cord compression. Skeletal-related events are major source of morbidity for cancer patients and may be associated with negative impact on quality of life and survival. Bisphosphonates inhibit osteoclast function and are widely used in the treatment of malignant bone disease, as preventive therapy against skeletal-related events. Recently, the NF-κappa B-ligand (RANKL)-mediated osteoclast activity and this pathway in bone metabolism became a prime target for the treatment of bone metastases. The fi rst drug targeting the RANK-RANKL pathway is denosumab, a fully monoclonal human antibody which binds to RANKL and inhibits osteoclast activity. Nowadays optimal treatment of bone metastases requires multidisciplinary management of patients including the administration of bone-modifying agents such bisphosphonates or denosumab. The use of bone-targeted agents is a valuable additional treatment in the fi ght against bone metastases and multiple, randomised trials have demonstrated the effectivity of these drugs in reducing skeletal morbidity caused by advanced cancer.]

COMMENTS

0 comments

Further articles in this publication

Clinical Oncology

[Tyrosine-kinase inhibitors and bisphosphonates in the treatment of metastases from renal cell carcinoma]

EDUARD Vrdoljak, TOMISLAV Omrčen

[Bone metastases (BMs) are common in patients with renal cell carcinoma (RCC) and approximately in 30% of patients with metastatic RCC (mRCC) will develop. Inhibition of vascular endothelial growth factor (VEGF) has been pursued as a therapeutic target in the treatment of metastatic clear cell RCC (mRCC). Tyrosine kinase inhibitors (TKIs), such as sunitinib, pazopanib, sorafenib, and axitinib, became the therapy of choice for patients with mRCC. Apart from the undisputed effi cacy of TKI in treatment of mRCC, the problem of metastatic bone disease still remains. There is evidence that the presence of BMs in m-RCC patients has a signifi cant and clinically-relevant negative impact on survival and potentially on the outcome of VEGF-targeted therapy. Also, common practice in the treatment of such patients is bonedirected therapy with BPs. Recent evidence shows a potentially synergistic effect on effi cacy but also a potential impact on increased toxicity of combining TKIs and BPs. This review highlights the importance of this subject and aims to facilitate further research and optimize the treatment of this important and common group of RCC patients.]

Clinical Oncology

[Cardiovascular Side Effects of Anti-Cancer Therapies]

LANDHERR László, NAGY András Csaba, NAGYKÁLNAI Tamás

Clinical Oncology

[Immuno(onco)therapy – road to the future]

DANK Magdolna, SZENTMÁRTONI Gyöngyvér, OROSZ Zsuzsanna, TÓTH Andrea, TŐKÉS Tímea

[Our immune system fi ghts effectively against infections, but the same activity exists against invading cancer cells, as well. However, malignant tumors are able to escape from these mechanisms; therefore tumor cells become unrecognizable for the immune system. Immuno-oncology is a novel and innovative discipline, focusing on a long-term purpose: to enhance the immune-response against malignancies. The main goal is to stimulate the immune system to properly recognize and destroy malignant tumor cells. This approach is comprehensive, includes the initiation of antitumor immune-response and enhancing its controlling mechanisms, moreover, provides active, anti-tumor effector cells. Recent results of anticancer research highlighted a new era of oncology, which is based on targeted, personalized medicine over cytotoxic therapies, and mainly focusing on the rapidly evolving discipline of immuno-oncology.]

Clinical Oncology

[Clinical role of multigenic prognostic tests in breast cancer therapy]

GYŐRFFY Balázs

[Current clinical practice for breast cancer originates in “evidence based medicine”. In this, each tumor receives a therapy optimal for a given patient population - which might not be optimal for each individual patient. Multigenic tests determining expression of a set of genes can provide additional support in this decision process. Two such tests (MammaPrint and Prosigna) have already received FDA clearance. A number of additional test are commercially available (IHC4, Oncotype DX, EndoPredict, BCI). A common property of these assays is their utility in estrogen receptor positive early breast cancer. The main clinical problem answered by them is the necessity of adjuvant chemotherapy. To date, no reliable algorithm has been identifi ed capable to pinpoint the most effective chemotherapy combination for a given patient. Furthermore, there is no trustworthy test for triple negative breast cancer. The assays utilize different technologies (immunohistochemistry, gene chips, RT-PCR) and a discrepant list of genes - these result in discordance of the predictions for the individual patient. Despite these shortcomings, multigenic tests quickly gained foothold in breast cancer therapy decision process. Their utility is supported by the cost reduction for the health care providers by lowering the number of patients eligible for chemotherapy.]

Clinical Oncology

[Emergency radiotherapy in oncology]

HIDEGHÉTY Katalin, DOBI Ágnes, MÓZES Petra, CSERHÁTI Adrienn

[Emergent radiotherapy is requested in 3-5% of all malignancys either presenting as initial manifestation of an unknown tumor or due to the progression of a malignancy under treatment/follow up. In this situation high degree of suspicion, timely diagnosis and adequate treatment for tumor-related complications are crucial, in order to prevent life-threatening or disabling conditions, such as vena cava superior syndrome, spinal cord compression or increased intracranial pressure. After prompt recognition, fast diagnostics and general management are needed to achive stable status. Radiotherapy commenced in some hours can markedly reduce morbidity and mortality and affects the outcome. There are few evidences based recommendations available, but the differential approach according to the tumor type should be considered (i.e. chemotherapy for lymphomas and SCLC causing SVCS, and sugery in certain case of spinal cord compressions). Prognosis and life expectancy should be taken into account and the goals of care have to be explored during initial evaluation. For patients with poor prognosis short course irradiation must be performed with palliative dose, meanwhile in the case of longer life expectancy the fi rst fraction of emergent radiation can be continued with selective techniques up to curative doses, which may improve the survival and quality of life.]

All articles in the issue

Related contents

LAM KID

[Effect of zoledronic acid treatment on pain and quality of life in patients with metastatic bone disease suffering from breast and prostate cancer - Multicenter, prospective, observational study]

PÁPAI Zsuzsanna, LANDHERR László, SPEER Gábor

[INTRODUCTION - Metastatic bone disease is frequently associated with breast and prostate cancer. Bisphosphonate treatment of bone metastases is palliative: its primary goal is to relieve pain, while it's also important to decrease the risk of bone fractures, prolong survival and maintain physical activity of the patients. Pain is the most common symptom of bone metastases. PATIENTS AND METHODS - In total 845 patients were enrolled in our open, multicenter, prospective, observational study, the first of its kind in Hungary. The agent tested was zoledronic acid (Zometa®). Duration of the study was 20 months and its primary goal was to assess the correlation between pain and quality of life during the treatment of patients with bone metastases from breast or prostate carcinoma. RESULTS - During the 18 months of the study, the average intensity of pain, measured on the visual analog scale showed a 42% reduction (p<0.0001). By the end of the 18. month, the ratio of patients free of symptoms has increased by 15% and the number of patients with substantial complaints has decreased by 73%. CONCLUSION - Our study supports the observation published in the international literature that in patients with bone metastases from breast and prostate cancer, zoledronic acid treatment is beneficial for reducing pain and thus for improving quality of life.]

Lege Artis Medicinae

[Medicine-induced osteonecrosis of the jaw]

VASZILKÓ Mihály, CSÉPLŐ Krisztina, NÉMETH Zsolt, BARABÁS József, UJPÁL Márta

[INTRODUCTION - Bisphosphonates are often used in the treatment of osteoporosis and of certain tumors with bone defects. Thus their rare side effect, necrosis of the jaw becomes more and more frequent. CASE REPORT - Between September 2005 and March 2008 we have treated 40 patients with bisphosphonate induced osteonecrosis in the maxillofacial region at our hospital. From this group, we selected two cases where typical complications emerged. CONCLUSION - Based upon data from the international literature and on our own experiences, we would like to draw attention to the importance of prevention. If symptoms are emerging, referral to a specialized department prepared to the treatment of this condition is recommended.]

LAM KID

[The pathogenic and clinical significance of the RANK-RANKL-osteoprotegerin system in rheumatoid arthritis]

SZENTPÉTERY Ágnes, VÁNCSA Andrea, SZABÓ Zoltán, SZEKANECZ Zoltán

[Rheumatoid arthritis (RA) is characterised by increased local and generalised bone resorption, which manifests in the develoment of marginal erosions and generalised osteoporosis, respectively. An increasing number of data suggest that lymphocytes, proinflammatory cytokines and other mediators involved in inflammation contribute to arthritic bone resorption. Therefore, the term ‘osteoimmunology’ has also become widely used. In RA, Receptor Activator of Nuclear Factor kappa B (RANK) and its ligand (RANKL) play a crucial role in bone resorption. These proteins, which belong to the tumor necrosis factor a (TNF-a) receptor and TNF ligand superfamilies, respectively, activate osteoclasts while interacting with T cells, synovial fibroblasts and other cytokines (e.g. IL-1, IL-17), which results in bone resorption. Osteoprotegerin (OPG) is a decoy receptor that also belongs to the TNF receptor family and inhibits RANK-RANKL interactions. There is increased RANKL production and decreased OPG production in RA. The interaction of RANKL with IL-17 is particularly important. Regarding therapy, sulfasalazine, methotrexate and biological agents, especially TNF inhibitors suppress RANKL-mediated bone resorption and thus the development of joint erosions. RANKL-RANK interaction can be directly inhibited by recombinant OPG or anti-RANKL antibody (denosumab). Among these agents, denosumab gave promising results in experiments performed in animal models of arthritis. These were followed by a phase II human RA trial, which proved that denosumab decreased MRI erosion scores in RA.]

Clinical Oncology

[Tyrosine-kinase inhibitors and bisphosphonates in the treatment of metastases from renal cell carcinoma]

EDUARD Vrdoljak, TOMISLAV Omrčen

[Bone metastases (BMs) are common in patients with renal cell carcinoma (RCC) and approximately in 30% of patients with metastatic RCC (mRCC) will develop. Inhibition of vascular endothelial growth factor (VEGF) has been pursued as a therapeutic target in the treatment of metastatic clear cell RCC (mRCC). Tyrosine kinase inhibitors (TKIs), such as sunitinib, pazopanib, sorafenib, and axitinib, became the therapy of choice for patients with mRCC. Apart from the undisputed effi cacy of TKI in treatment of mRCC, the problem of metastatic bone disease still remains. There is evidence that the presence of BMs in m-RCC patients has a signifi cant and clinically-relevant negative impact on survival and potentially on the outcome of VEGF-targeted therapy. Also, common practice in the treatment of such patients is bonedirected therapy with BPs. Recent evidence shows a potentially synergistic effect on effi cacy but also a potential impact on increased toxicity of combining TKIs and BPs. This review highlights the importance of this subject and aims to facilitate further research and optimize the treatment of this important and common group of RCC patients.]

Ca&Bone

[Denosumab - pharmacokinetic and clinical evidences]

MÉSZÁROS SZILVIA

[Denosumab is a fully human monoclonal antibody to RANKL modifying bone resorption in a rapid, sustained and reversible way. In postmenopausal women with low bone mineral density, denosumab 60 mg every 6 months increased mineral density, and reduced bone turnover. In postmenopausal women, it reduced the risk of vertebral, hip, and non-vertebral fractures. Increase in body mass index and reduction in bone turnover was more pronounced with denosumab than with alendronate. In patients who were switched from alendronate to denosumab, positive effects on bone were more pronounced than in those continuing alendronate. Denosumab was safe and well tolerated, and it holds the promise of becoming an efficacious therapy for postmenopausal osteoporosis.]