Denosumab in Osteoporosis and Oncology
Prostate cancer; breast-cancer; osteoporosis; Pharmacology & Pharmacy; postmenopausal women; breast-cancer; bone-mineral density; tumor; metastases; ligand; biochemical markers; bisphosphonate therapy; bone metastases; denosumab; monoclonal antibody; multiple; myeloma; necrosis factor; phase-ii; RANKL; solid tumor; turnover; zoledronic acid
OBJECTIVE: To review the pharmacology, pharmacokinetics, pharmacodynamics, safety, efficacy, and use of denosumab in osteoporosis, breast cancer, prostate cancer, and multiple myeloma. DATA SOURCES: Studies and abstracts were identified through MEDLINE and International Pharmaceutical Abstracts (1966-July 2009). Key search terms include denosumab, AMG-162, and receptor activator of nuclear factor-kappa B ligand system. Information available in abstract form was retrieved from major oncology and bone metabolism meetings. Additional data were obtained from the manufacturer. STUDY SELECTION AND DATA EXTRACTION: All available studies in humans were included except for studies in rheumatoid arthritis and giant cell tumor of the bone. DATA SYNTHESIS: In patients with osteoporosis, denosumab significantly reduces bone resorption and fractures. Studies of denosumab in the prevention and treatment of osteoporosis have demonstrated significantly increased bone mineral density and reduced bone turnover markers. Studies of denosumab versus placebo in the treatment of osteoporosis have demonstrated reductions in vertebral, hip, and nonvertebral fractures. In oncology, positive results from clinical trials in patients receiving endocrine therapy for breast and prostate cancer demonstrated decreases in bone loss and skeletal-related events. Denosumab seems to be at least as effective in reducing bone turnover markers as intravenous bisphosphonates in the oncology setting. The most common adverse effects in patients with osteoporosis were arthralgia, nasopharyngitis, back pain, and headache. The most common adverse effects in patients with cancer were infection, pain in the extremities, arthralgia, bone pain, fatigue, and pain. Serious adverse effects include infections requiring hospitalization. CONCLUSIONS: Denosumab has documented efficacy and safety in patients with osteoporosis, breast cancer, and prostate cancer. Additional clinical trial data are needed to more completely establish the effectiveness of denosumab in the treatment of osteoporosis and neoplastic disease as well as its cost-effectiveness and long-term safety.
Burkiewicz J S; Scarpace S L; Bruce S P
Annals of Pharmacotherapy
2009
2009-09
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1345/aph.1M102" target="_blank" rel="noreferrer noopener">10.1345/aph.1M102</a>
Predictive model for survival in patients having repeat radiation treatment for painful bone metastases.
*Models; Aged; Bone metastases; Bone Neoplasms/*mortality/*radiotherapy/secondary; Dose Fractionation; Female; Humans; Male; Middle Aged; Predictive model; Predictive Value of Tests; Proportional Hazards Models; Radiation; Randomized Controlled Trials as Topic/methods; Re-irradiation; Statistical; Survival; Survival Analysis; Survival Rate
PURPOSE: To establish a survival prediction model in the setting of a randomized trial of re-irradiation for painful bone metastases. METHODS: Data were randomly divided into training and testing sets with an approximately 3:2 ratio. Baseline factors of gender, primary cancer site, KPS, worst-pain score and age were included with backward variable selection to derive a model using the training set. A partial score was assigned by dividing the value of each statistically significant regression coefficient by the smallest statistically significant regression coefficient. The survival prediction score (SPS) was obtained by adding together partial scores for the variables that were statistically significant. Three risk groups were modelled. RESULTS: The training set included 460 patients and the testing set 351 patients. Only KPS and primary cancer site reached the 5%-significance level. Summing up the partial scores assigned to KPS (90-100, 0; 70-80, 1; 50-60, 2) and primary cancer site (breast, 0; prostate, 1.3; other, 2.6; lung, 3) totalled the SPS. The 1/3 and 2/3 percentiles of the SPS were 2 and 3.6. For the testing set, the median survival of the 3 groups was not reached, 11.3 (95% C.I. 8.5 - not reached) and 5.2 months (95% C.I. 3.7-6.5). The 3, 6 and 12 month survival rates for the worst group were 64.4% (95% C.I. 55.3-72.1%), 43.0% (95% C.I. 34.0-51.8%) and 19.7% (95% C.I. 12.4-28.1%) respectively, similar to that in the training set. CONCLUSION: This survival prediction model will assist in choosing dose fractionation. We recommend a single 8 Gy in the worst group identified.
Chow Edward; Ding Keyue; Parulekar Wendy R; Wong Rebecca K S; van der Linden Yvette M; Roos Daniel; Hartsell William F; Hoskin Peter; Wu Jackson S Y; Nabid Abdenour; Leer Jan Willem; Vonk Ernest; Babington Scott; Demas William F; Wilson Carolyn F; Brundage Michael; Zhu Liting; Meyer Ralph M
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
2016
2016-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.radonc.2015.10.018" target="_blank" rel="noreferrer noopener">10.1016/j.radonc.2015.10.018</a>
Revisiting classification of pain from bone metastases as mild, moderate, or severe based on correlation with function and quality of life.
*Quality of Life; *Severity of Illness Index; 80 and over; 80 and Over; Adolescence; Adolescent; Adult; Aged; Bone metastases; Bone Neoplasms; Bone Neoplasms – Complications; Bone Neoplasms/*complications/secondary; Brief Pain Inventory; Female; Functional interference; Funding Source; Human; Humans; Male; Middle Age; Middle Aged; Pain – Classification; Pain – Etiology; Pain Measurement – Methods; Pain Measurement/*methods; Pain severity; Pain/*classification/etiology; Quality of life; Quality of Life; Questionnaires; Re-irradiation; Severity of Illness Indices; Survival; Young Adult
PURPOSE: The objective of our study was to determine the optimal cut points for classification of pain scores as mild, moderate, and severe based on interference with function and quality of life (QOL). METHODS: We evaluated 822 patients who completed the Brief Pain Inventory (BPI) and/or the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 30 (QLQ-C30) prior to receiving repeat radiation therapy for previously irradiated painful bone metastases. Optimal cut points for mild, moderate, and severe pain were determined by the MANOVA that yielded the largest F ratio for the between category effect on the seven interference items of BPI and the six functional domains of QOL (physical, role, emotional, cognitive, social functioning, and global QOL) as indicated by Pillai's Trace, Wilk's lambda, and Hostelling's Trace F statistics. RESULTS: For BPI and for QOL domains separately, the two largest F ratios for Wilk's lambda, Pillai's Trace, and Hotelling's Trace F statistics were from the cut points 4, 8 and 6, 8. When combining both, the optimal cut points were 4, 8 with 1-4 (mild), 5-8 (moderate), and 9-10 (severe). With this classification, the mean scores of all the seven interference items in BPI and the six functional domains were all highly statistically different. Patients with severe pain survived significantly shorter than those with mild and moderate pain (p \textless 0.0001). CONCLUSION: Our analysis supports the classification of pain scores as follows: 1-4 as mild pain, 5-8 as moderate pain, and 9-10 as severe pain. This may facilitate conduct of future clinical trials.
Chow Edward; Ding Keyue; Parulekar Wendy R; Wong Rebecca K S; van der Linden Yvette M; Roos Daniel; Hartsell William F; Hoskin Peter; Wu Jackson S Y; Nabid Abdenour; Ong Francisca; van Tienhoven Geertjan; Babington Scott; Demas William F; Wilson Carolyn F; Brundage Michael; Zhu Liting; Meyer Ralph M
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
2016
2016-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00520-015-2957-5" target="_blank" rel="noreferrer noopener">10.1007/s00520-015-2957-5</a>