nach oben

Current Oncology Reports

Erschienen in:

01.02.2011

Denosumab in Breast Cancer

verfasst von: Allan Lipton

Erschienen in: Current Oncology Reports | Ausgabe 1/2011

Einloggen, um Zugang zu erhalten

Abstract

Bone destruction is mediated by osteoclasts, whose formation, function, and survival requires the receptor activator of NF-kB ligand (RANKL). Denosumab is a fully human monoclonal antibody to RANKL, thereby inhibiting osteoclast-mediated bone destruction, and blocks the vicious cycle of cancer-mediated bone disease. In breast cancer patients with bone metastases, denosumab was superior to zoledronic acid in delaying time to first on-study skeletal-related event (SRE; HR = 0.82; P = 0.01 superiority) and time to first and subsequent on-study SREs (HR = 0.77; P = 0.001). Overall survival, disease progression, and serious adverse events were similar between groups.

Coleman RE: Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 2006, 12:6243s–6249s.CrossRefPubMed

Lipton A, Cook RJ, Major P, et al.: Zoledronic acid and survival in breast cancer patients with bone metastases and elevated markers of osteoclast activity. Oncologist 2007, 12:1035–1043.CrossRefPubMed

Rodan GA: The development and function of the skeleton and bone metastases. Cancer 2003, 97:726–732.CrossRefPubMed

Roodman GD: Mechanisms of bone metastasis. N Engl J Med 2004, 350:1655–1664.CrossRefPubMed

Lacey DL, Timms E, Tan HL, et al.: Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998, 93:165–176.CrossRefPubMed

Lacey DL, Tan HL, Li J, et al.: Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Am J Pathol 2000, 157:435–448.PubMed

Simonet WS, Lacey DL, Dunstan CR, et al.: Osteoprotegerin is a novel secreted protein involved in the regulation of bone density. Cell 1997, 89:309–319.CrossRefPubMed

Fuller K, Wong B, Fox S, et al.: TRANCE is necessary and sufficient for osteoblast-mediated activation of bone resorption in osteoclasts. J Exp Med 1998, 188:997–1000.CrossRefPubMed

Yasuda H, Shima N, Nakagava N, et al.: Osteoclast differentiation factor is a ligand for osteoprotegerin in osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 1998, 95:3597–3601.CrossRefPubMed

10.

Yasuda J, Shima N, Nakagawa N, et al.: Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG:OCIF inhibits osteoclastogenesis in vitro. Endocrinology 1998, 139:1329–1337.CrossRefPubMed

11.

Yasuda H, Shima N, Nakagawa N, et al.: A novel molecular mechanism modulating osteoclast differentiation and function. Bone 1999, 25:109–113.CrossRefPubMed

12.

Blair JM, Zhou H, Seibel MJ, et al.: Mechanisms of disease roles of OPG, RANKL and RANK in the pathophysiology of skeletal metastasis. Nat Clin Pract Oncol 2006, 3:41–49.CrossRefPubMed

13.

Clines GA, Guise TA: Hypercalcemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone. Endo Relat Cancer 2005, 12:549–583.CrossRef

14.

Guise TA, Mohammad KS, Clines G, et al.: Basic mechanisms responsible for osteolytic and osteoblastic bone metastases. Clin Cancer Res 2006, 12:6213s–6216s.CrossRefPubMed

15.

Shapiro CL, Manoola J, Lbeoff M: Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in women with early-stage breast cancer. J Clin Oncol 2001, 19:3306–3311.PubMed

16.

• Hadji P, Ziller M, Kieback DG, et al.: Effects of exemestane and tamoxifen on bone health within the Tamoxifen Exemestane Adjuvant Multicentre (TEAM) trial: results of a German, 12-month, prospective, randomized substudy. Ann Oncol 2009, 20:1203–1209. This study highlights the bone loss that accompanies treatment with an aromatase inhibitor. CrossRefPubMed

17.

Mincey GA, Duh MS, Thomas SK, et al.: Risk of cancer treatment-associated bone loss and fractures among women with breast cancer receiving aromatase inhibitors. Clin Breast Cancer 2006, 7:127–132.CrossRefPubMed

18.

• Eastell R, Adams JE, Coleman RE, et al.: Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen alone or in combination trial. J Clin Oncol 2008, 26:1051–1057. This article details the importance of bone loss associated with long-term treatment (5 years) with an aromatase inhibitor. CrossRefPubMed

19.

Morony S, Capparelli C, Sarosi I, et al.: Osteoprotegerin inhibits osteolysis and decreases skeletal tumor burden in syngeneic and nude mouse models of experimental bone metastasis. Cancer Res 2001, 61:4432–4436.PubMed

20.

Lipton A, Steger GG, Figueroa J, et al.: Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases. J Clin Oncol 2007, 25:4431–4435.CrossRefPubMed

21.

• Fizazi K, Lipton A, Mariette X, et al.: Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol 2009, 27:1564–1572. This article reports results of a trial comparing denosumab with continued zoledronic acid in patients who have high bone resorption on bisphosphonate therapy. CrossRefPubMed

22.

• Ellis GK, Bone HG, Chlebowski R, et al.: Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol 2008, 26:4875–4882. This article found that denosumab prevents loss of BMD associated with aromatase inhibitor therapy. CrossRefPubMed

23.

Hosking D, Chilvers CE, Christiansen C, et al.: Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group. N Engl J Med 1998, 338:485–492.CrossRefPubMed

24.

• Stopeck AT, Lipton A, Body JJ, et al.: Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: A randomized, double-blind study. J Clin Oncol 2010, In press. This article reports results from a phase 3 trial comparing denosumab versus zoledronic acid in patients with breast cancer and bone metastases.

Titel: Denosumab in Breast Cancer
verfasst von: Allan Lipton
Publikationsdatum: 01.02.2011
Verlag: Current Science Inc.
Erschienen in: Current Oncology Reports / Ausgabe 1/2011
Print ISSN: 1523-3790
Elektronische ISSN: 1534-6269
DOI: https://doi.org/10.1007/s11912-010-0135-y

Springer Medizin

Denosumab in Breast Cancer

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2011

The Need to Examine Metastatic Tissue at the Time of Progression of Breast Cancer: Is Re-biopsy a Necessity or a Luxury?

Breast Cancer Screening with Mammography

Chemoradiotherapy for Cervical Cancer in 2010

Tumor Profiling: Development of Prognostic and Predictive Factors to Guide Brain Tumor Treatment

Response Assessment in Neuro-Oncology

The Need for Axillary Dissection in Patients with Positive Axillary Sentinel Lymph Nodes

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie