Treatment Of Skeletal Complications Research Articles

CApecitabine plus Radium-223 (Xofigo\u2122) in breast cancer patients with BONe metastases (CARBON): study protocol for a phase IB/IIA randomised controlled trial

BackgroundA substantial proportion of breast cancer patients develop metastatic disease, with over 450,000 deaths globally per year. Bone is the most common first site of metastatic disease accounting for 40% of all first recurrence and 70% of patients with advanced disease develop skeletal involvement.Treatment of bone metastases currently focusses on symptom relief and prevention and treatment of skeletal complications. However, there remains a need for further treatment options for patients with bone metastases. Combining systemic therapy with a bone-targeted agent, such as radium-223, may provide an effective treatment with minimal additional side effects.Methods/designCARBON is a UK-based, open-label, multi-centre study which comprises an initial safety phase to establish the feasibility and safety of combining radium-223 given on a 6-weekly schedule in combination with orally administered capecitabine followed by a randomised extension phase to further characterise the safety profile and provide preliminary estimation of efficacy.DiscussionThe CARBON study is important as the results will be the first to assess radium-223 with chemotherapy in advanced breast cancer. If the results find acceptable rates of toxicity with a decrease in bone turnover markers, further work will be necessary in a phase II/III setting to assess the efficacy and clinical benefit.Trial registrationISRCTN, ISRCTN92755158, Registered on 17 February 2016.

The Effect of Alendronate on Proteome of Hepatocellular Carcinoma Cell Lines

Cancer is a life threatening disorder effecting 11 million people worldwide annually. Among various types of cancers, Hepatocellular carcinoma (HCC) has a higher rate of mortality and is the fifth leading cause of cancer related deaths around the world. Many chemotherapeutic drugs have been used for the treatment of HCC with many side effects. These drugs are inhibitors of different cell regulatory pathways. Mevalonate (MVA) pathway is an important cellular cascade vital for cell growth. A variety of inhibitors of MVA pathway have been reported for their anticancerous activity. Bisphosphonates (BPs) are members of a family involved in the treatment of skeletal complications. In recent years, their anticancer potential has been highlighted. Current study focuses on exploring the effects of alendronate (ALN), a nitrogen containing BP, on hepatocellular carcinoma cell line using genomic and proteomics approach. Our results identified ten differentially expressed proteins, of which five were up regulated and five were down regulated in ALN treated cells. Furthermore, we also performed gene expression analysis in treated and control cell lines. The study may help in understanding the molecular mechanism involved in antitumor activity of ALN, identification of possible novel drug targets, and designing new therapeutic strategies for HCC.

Physiopathologie et nouvelles stratégies thérapeutiques dans la prise en charge des métastases osseuses du cancer de la prostate

Prostate cancer (PCa) is one of the most common human malignancies that have a strong propensity to spread in the bones. Despite the progress in the diagnosis and the treatment of prostate cancer, bone metastases are present in nearly 95% of men with metastatic PCa at autopsy. Bone metastases are a major cause of skeletal complications which may negatively affect the quality of life and increase morbidity and mortality in men with advanced PCa. Bisphosphonates are potent inhibitors of bone resorption that have demonstrated clinical benefit for the treatment of bone metastases. They are standard of care for the prevention of skeletal complications such as pain and pathological fractures in patients with bone metastases from PCa. More recently, the discovery of the OPG/RANK/RANKL system has permitted to better understand the role of OPG and RANKL as key regulators of osteoclast-mediate bone destruction in both normal bone remodelling and pathologic conditions. RANKL has been shown to contribute to the vicious cycle of bone destruction and tumour growth in PCa. Therefore, the development of new emerging treatment that inhibits RANKL using RANKL antibodies, as denosumab, resulted in a better control and treatment of skeletal complications, with the hope in a near future to prevent bone metastases.

Bisphosphonate-Induced Osteonecrosis of the Jaw 32 Months After Interruption of Zoledronate in a Patient With Multiple Myeloma

Bisphosphonates prevent, reduce, and delay cancer-related skeletal complications in patients with multiple myeloma or metastatic cancer. 1 Rosen L.S. Gordon D. Kaminski M. et al. Long-term efficacy and safety of zoledronic acid compared with pamidonate disodium in treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: A randomized, double-blind, multicenter, comparative trial. Cancer. 2003; 98: 1735 Crossref PubMed Scopus (756) Google Scholar Thus, the therapy is commonly prescribed to patients with multiple myeloma. 2 Kyle R.A. Yee G.C. Somerfield M.R. et al. American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin Oncol. 2007; 25: 2464 Crossref PubMed Scopus (356) Google Scholar Bisphosphonates are extremely effective in reducing the symptoms and complications of bone lesions and have been shown to have a profound effect on the quality of life of patients with multiple myeloma. However, in the past few years, several reports and recommendations have been published about bisphosphonate-induced osteonecrosis of the jaw (BRONJ) since the first reports were published in 2003 as a potential adverse effect of Zometa (zoledronic acid; Novartis, East Hanover, NJ). 3 Migliorati C.A. Bisphosphonates and oral cavity avascular bone necrosis. J Clin Oncol. 2003; 21: 4253 Crossref PubMed Scopus (429) Google Scholar , 4 Marx R.E. Pamidronate (Aredia) and zolendronate (Zometa) induced avascular necrosis of the jaws: A growing epidemic. J Oral Maxillofac Surg. 2003; 61: 1115 Abstract Full Text Full Text PDF PubMed Scopus (2095) Google Scholar , 5 Ruggiero S.L. Mehrotra B. Rosenberg T.J. et al. Osteonecrosis of the jaws associated with the use of bisphosphonates: A review of 63 cases. J Oral Maxillofac Surg. 2004; 62: 527 Abstract Full Text Full Text PDF PubMed Scopus (1609) Google Scholar It was observed that the major risk factors are dental extraction and the therapy duration with zoledronic acid. 6 Advisory Task Force on Bisphosphonate-Related Osteonecrosis of the JawsAmerican Association of Oral and Maxillofacial Surgeons' position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg. 2007; 65: 369 Abstract Full Text Full Text PDF PubMed Scopus (740) Google Scholar BRONJ was often diagnosed during or after therapy (range, 1 to 13 months). 7 Ibrahim T. Barbati F. Giorgio-Marrano G. et al. Osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates: A retrospective study. Oncologist. 2008; 13: 330 Crossref PubMed Scopus (55) Google Scholar We report an extensive case of BRONJ that was clinically evident more than 32 months after the suspension of zoledronic acid.

Zoledronic acid in the management of metastatic bone disease.

Many patients with advanced cancer experience decreased bone strength due to metastatic foci, underlying osteoporosis and/or cancer treatment induced bone loss. The clinical consequences of metastatic disease involving the skeleton are widespread. This review focuses on the efficacy, pharmacology, and safety when using intravenous biphosphonate such a zoledronic acid for cancer bone metastases. Zoledronic acid is the gold standard for the medical management of metastatic bone disease. The indications for treatment include prevention of skeletal relevant events (SRE), osteoporotic complications, and palliation of bone pain, among others. Zoledronic acid is the only bisphosphonate effective in decreasing SREs associated with bone metastases from advanced renal cell carcinoma and prostate cancer. Regarding prostate cancer, zoledronic acid effectively prevents both bone loss in patients with locally advanced disease receiving androgen deprivation therapy and SREs in men with hormone-refractory or hormone-sensitive metastatic disease. Zoledronic acid has an acceptable safety profile and tolerability, and has been effective at significantly decreasing the incidence, delaying the onset, and reducing the overall risk of experiencing an SRE compared to placebo. It is the only bisphosphonate currently approved for the prevention and treatment of skeletal complications in patients with bone metastases due to all solid tumors.

Use of bisphosphonates can dramatically improve pain in advanced hormone-refractory prostate cancer patients

Approximately 85% of patients who die from prostate cancer present the spread of bone metastases. Even though the radiological appearance of such metastases is osteoblastic, it is now known that these lesions coexist in their microenvironment with blastic and lytic lesions. The process always begins with bone lysis by osteoclast proliferation, paralleling nearby bone deposition. The treatment options are palliative and have poor clinical response with short-lived improvement. We have studied the clinical effect of bisphosphonates (clodronate) in the treatment of skeletal complications from prostate cancer. In an open prospective study, 58 patients with hormone-refractory prostate cancer with bone metastases were assessed from November 2000 to September 2003. The mean age was 70.3 y (range: 51-87 y). Bone scintigraphy, plain X-ray, assaying of prostate-specific antigen (PSA) and biochemical tests were requested before and following treatment. Patients were previously and subsequently assessed using the visual pain scale (0-10) and Karnofsky's index after the first and second intravenous (i.v.) infusions (administration of i.v. clodronate every 28 days) and every 4-6 months thereafter. Student's t-test was used for statistical analysis. A total of 53 patients (91.4%) showed improvement after the first and/or second cycle, which persisted for at least 4 months (average 6.3 months). The averages on the visual pain scale improved from 7.4 (range: 2-8) to 2.4 (0-7) and on Karnofsky's index from 43 (32-58) to 73 (50-82). The radiological appearance of the metastases improved in 27 patients (46.5%) and there were few relapses (six patients; 10.3%). Clodronate was effective in the treatment of skeletal complications from prostate cancer. There was an objective response in 91.4% of treated patients, with a marked improvement in the subjective visual pain scale evaluation as well as on Karnofsky's index, with low side effects.

Managing cancer-related skeletal events with bisphosphonates.

Bone metastases cause considerable morbidity. This article discusses the benefits of bisphosphonates, which are now well established in the treatment of skeletal complications across a wide range of tumour types.

Biochemical markers and skeletal metastases.

Bisphosphonate therapy for the treatment of skeletal complications from osteolytic metastases has become standard care in patients with cancer who have metastatic bone disease. The ability to assess patient response to bisphosphonate therapy has been helped by the availability of immunoassays that can measure bone collagen breakdown products that are increased in the blood and urine of patients with osteolytic metastases. Measurements of the carboxy and amino terminal telopeptides in blood and urine particularly have been helpful as adjunct methods to facilitate the treatment of patients with skeletal metastases. These biochemical bone markers have been shown to correlate with the extent of skeletal involvement and seem to provide a means of monitoring the dose and scheduling of bisphosphonate therapy of patients with cancer who have bony metastases.