Pamidronate Reduces Skeletal Morbidity in Women With Advanced Breast Cancer and Lytic Bone Lesions: A Randomized, Placebo-Controlled Trial

1999 ◽  
Vol 17 (3) ◽  
pp. 846-846 ◽  
Author(s):  
Richard L. Theriault ◽  
Allan Lipton ◽  
Gabriel N. Hortobagyi ◽  
Richard Leff ◽  
Stefan Glück ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormonal Therapy ◽  
Intravenous Infusion ◽  
Bone Lesion ◽  
Morbidity Rate ◽  
Bone Lesions ◽  
Skeletal Complication ◽  
Pathologic Fractures ◽  
Bone Response ◽  
Skeletal Complications

PURPOSE: To assess whether pamidronate can reduce the frequency of skeletal morbidity in women with lytic bone metastases from breast cancer treated with hormone therapy. PATIENTS AND METHODS: Three hundred seventy-two women with breast cancer who had at least one lytic bone lesion and who were receiving hormonal therapy were randomized to receive 90 mg of pamidronate or placebo as a 2-hour intravenous infusion given in double-blind fashion every 4 weeks for 24 cycles. Patients were evaluated for skeletal complications: pathologic fractures, spinal cord compression, irradiation of or surgery on bone, or hypercalcemia. The skeletal morbidity rate (the ratio of the number of skeletal complications to the time on trial) was the primary efficacy variable. Bone pain, use of analgesics, quality of life, performance status, bone tumor response, and biochemical parameters were also evaluated. RESULTS: One hundred eighty-two patients who received pamidronate and 189 who received placebo were assessable. The skeletal morbidity rate was significantly reduced at 12, 18, and 24 cycles in patients treated with 90 mg of pamidronate (P = .028, .023, and .008, respectively). At 24 cycles, the proportion of patients having had any skeletal complication was 56% in the pamidronate group and 67% in the placebo group (P = .027). The time to the first skeletal complication was longer for patients receiving pamidronate than for those given placebo (P = .049). There was no statistical difference in survival or in objective bone response rate. Pamidronate was well tolerated. CONCLUSION: Treatment with 90 mg of pamidronate as a 2-hour intravenous infusion every 4 weeks in addition to hormonal therapy significantly reduces skeletal morbidity from osteolytic metastases.

Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. Protocol 19 Aredia Breast Cancer Study Group.

1998 ◽  
Vol 16 (6) ◽  
pp. 2038-2044 ◽  
Author(s):  
G N Hortobagyi ◽  
R L Theriault ◽  
A Lipton ◽  
L Porter ◽  
D Blayney ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Placebo Group ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Bone Lesions ◽  
Skeletal Complication ◽  
Lytic Bone Lesions ◽  
Skeletal Complications ◽  
Bone Complications

PURPOSE Pamidronate, an aminobisphosphonate, has been shown to lower the risk of skeletal complications associated with lytic bone lesions for up to 1 year in women with stage IV breast cancer who received chemotherapy. We studied the long-term effectiveness and safety of continued treatment with intravenous pamidronate infusions for up to 2 years. PATIENTS AND METHODS Three hundred eighty-two women with metastatic breast cancer and lytic bone lesions who received chemotherapy were randomly assigned to receive either 90 mg of pamidronate or placebo intravenously every 3 to 4 weeks in this double-blind, multicenter, parallel-group trial. Patients were evaluated monthly for 2 years for skeletal complications, which included pathologic fractures, need for radiation or surgery to treat bone complications, spinal cord compression, and hypercalcemia. Bone pain, analgesic use, bone biochemical markers, performance status, quality of life, radiologic response in bone, and survival were also evaluated. RESULTS As in the first year of treatment, the proportion of patients with any skeletal complication was significantly less for the pamidronate than the placebo group at 15, 18, 21, and 24 months (P < .001). The proportions of patients with any pathologic fracture (i.e., vertebral and nonvertebral fractures), need for radiation or surgery to treat bone complications, and hypercalcemia were also statistically less for the pamidronate than the placebo group. The median time to the first skeletal complication was 13.9 months in the pamidronate-treated women and 7.0 months in the placebo group (P < .001). Long-term treatment did not result in any unexpected adverse events. Survival did not differ between the two groups. CONCLUSION The risk for osteolytic bone lesion complications in metastatic breast cancer was significantly decreased with monthly infusions of 90 mg of pamidronate, and this effect was maintained for at least 2 years. Pamidronate is a useful adjunct to standard chemotherapy in the palliative treatment of metastatic breast cancer.

Micro-imaging characterization of mouse models of metastasis

2005 ◽  
Author(s):  
◽  
Christopher Todd Winkelmann
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Mouse Models ◽  
Bone Lesion ◽  
Receptor Expression ◽  
Bone Lesions ◽  
Micro Ct ◽  
Peptide Receptor ◽  
Gastrin Releasing Peptide ◽  
Models Of Disease

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Non-invasive imaging techniques have been recently developed to characterize animal models of disease. The overarching hypothesis of this work explores the use of three micro-imaging modalities, including Micro-CT, PET and SPECT, to characterize tumor anatomical progression, metabolism, bone lesion remodeling, and/or gastrin releasing peptide receptor expression in mouse models of metastatic melanoma and prostate and breast cancer bone metastasis. Micro-CT was shown to provide excellent anatomical information about tumor progression in several different tissues including lung, bone, and subcutaneous tissues. Micro-PET imaging demonstrated increased tumor metabolism in melanoma tumors, but was not able to discern bone remodeling in breast cancer bone lesions. Micro-SPECT imaging demonstrated gastrin-releasing peptide receptor expression in a prostate cancer bone metastasis model. The results from this work demonstrate the ability of micro-imaging technologies to non-invasively probe mouse models of disease to obtain information in vivo that is not possible with ex vivo experimental techniques.

Pamidronate in Prevention of Bone Complications in Metastatic Breast Cancer: A Cost-Effectiveness Analysis

2000 ◽  
Vol 18 (1) ◽  
pp. 72-72 ◽  
Author(s):  
Bruce E. Hillner ◽  
Jane C. Weeks ◽  
Christopher E. Desch ◽  
Thomas J. Smith
Keyword(s):  
Breast Cancer ◽  
Adverse Event ◽  
Metastatic Breast Cancer ◽  
Cost Effectiveness ◽  
Hormonal Therapy ◽  
Systemic Therapy ◽  
Metastatic Breast ◽  
Pathologic Fracture ◽  
Pathologic Fractures ◽  
The Cost

PURPOSE: Pamidronate is effective in reducing bony complications in patients with metastatic breast cancer who have known osteolytic lesions. However, pamidronate does not increase survival and is associated with additional financial costs and inconvenience. We conducted a post-hoc evaluation of the cost-effectiveness of pamidronate using the results of two randomized trials that evaluated pamidronate 90 mg administered intravenously every month versus placebo. PATIENTS AND METHODS: The trials differed only in the initial systemic therapy administered (hormonal or chemotherapy). Total skeletal related events (SREs), including surgery for pathologic fracture, radiation for fracture or pain control, conservatively treated pathologic fracture, spinal cord compression, or hypercalcemia, were taken directly from the trials. Using a societal perspective, direct health care costs were assigned to each SRE. Each group’s monthly survival was equal and was projected to decline using observed median survivals. The cost of pamidronate reflected the average wholesale price of the drug plus infusion. The value or disutility of an adverse event per month was evaluated using a zero value (events avoided) or an assigned one (range, 0.2 to 0.8). RESULTS: The cost of pamidronate therapy exceeded the cost savings from prevented adverse events. The difference between the treated and placebo groups was larger with hormonal systemic therapy than with chemotherapy (additional $7,685 compared with $3,968 per woman). The projected net cost per SRE avoided was $3,940 with chemotherapy and $9,390 with hormonal therapy. The cost-effectiveness ratios were $108,200 with chemotherapy and $305,300 with hormonal therapy per quality-adjusted year. CONCLUSION: Although pamidronate is effective in preventing a feared, common adverse outcome in metastatic breast cancer, its use is associated with high incremental costs per adverse event avoided. The analysis is most sensitive to the costs of pamidronate and pathologic fractures that were asymptomatic or treated conservatively.

scholarly journals Metastatic Bone Disease in Patients with Solid Tumors–-Burden of Bone Disease and the Role of Zoledronic Acid

2009 ◽  
Vol 1 ◽  
pp. CMT.S1958
Author(s):  
Vera Hirsh
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Bone Disease ◽  
Large Scale ◽  
Comparative Trial ◽  
Palliative Radiotherapy ◽  
Bone Lesions ◽  
Pathologic Fractures

Bisphosphonates have become an integral component of the therapeutic repertoire for cancer patients at risk for skeletal-related events (SREs) such as pathologic fractures, bone pain requiring palliative radiotherapy, the need for orthopedic surgery, spinal cord compression, and hypercalcemia of malignancy because of bone metastases. Administered via monthly 15-minute infusion of up to 4 mg (depending on creatinine clearance rate), zoledronic acid (ZOL) has been approved for preventing SREs in patients with bone metastases from any solid tumor or bone lesions from multiple myeloma. Although there have been limited head-to-head comparison trials between bisphosphonates, ZOL displayed benefits beyond pamidronate in a large-scale comparative trial in patients with bone metastases from breast cancer. Monitoring of serum creatinine levels and oral health is important to ensure safety and comfort during treatment. In addition to the established benefits of bisphosphonates in the advanced cancer setting, there is a strong preclinical rationale and emerging clinical evidence that ZOL has antitumor activities and can delay metastasis in patients with early breast cancer. Studies are underway in patients with other tumor types, and the role of bisphosphonates is likely to evolve.

Zoledronic Acid May Improve Survival Compared to Pamidronate in Patients with MM and High BALP Levels: Univariate and Multivariate Models of Hazard Ratios.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3589-3589 ◽  
Author(s):  
James R. Berenson ◽  
Meletios A. Dimopoulos ◽  
Yin-Miao Chen
Keyword(s):  
Multiple Myeloma ◽  
Zoledronic Acid ◽  
Bone Metabolism ◽  
Cox Regression ◽  
Multivariate Analyses ◽  
Bone Lesions ◽  
Multivariate Models ◽  
Risk Of Death ◽  
Pathologic Fractures ◽  
Skeletal Complications

Abstract In untreated patients with multiple myeloma, elevated bone-specific alkaline phosphatase (BALP) levels have shown a significant association with bone pain, bone lesions, and pathologic fractures, and have been correlated with reduced survival (Fonseca R, et al. Br J Haemotol.2000;109:24–29). Zoledronic acid reduces the risk of skeletal morbidity and levels of biochemical markers of bone metabolism in patients with bone lesions from multiple myeloma. Zoledronic acid has also demonstrated antimyeloma effects in preclinical studies in vitro and in vivo using mice bearing human or mouse myeloma. Therefore, it is possible that zoledronic acid may not only prevent skeletal complications but also increase survival in patients with multiple myeloma. We conducted a retrospective exploratory analysis of patients with multiple myeloma and bone lesions as part of a large, randomized, controlled trial comparing infusions of zoledronic acid 4 mg and pamidronate 90 mg to assess the effect of zoledronic acid on survival based on baseline bone marker levels. In the overall population of patients with multiple myeloma (N=353), survival was comparable between groups. The subset of multiple myeloma patients who had information on baseline BALP levels were examined in these analyses (n=212; 4 mg zoledronic acid [n=109] or 90 mg pamidronate [n=103]). Patients received treatment for up to 24 months with a final assessment at 25 months. Risk of death was assessed in univariate and multivariate models using Cox regression methodology. Factors included in the multivariate analyses were prior skeletal-related events and baseline ECOG performance status. Among patients who had a baseline BALP assessment, zoledronic acid significantly increased the 25-month overall survival compared with pamidronate (76% versus 63%; P=.026). In the univariate and multivariate analyses, zoledronic acid significantly reduced the risk of death by approximately 42% compared with pamidronate (P=.03 for both). The subset of patients was then retrospectively stratified by baseline BALP levels according to the following criteria: low BALP (<146 U/L) and high BALP (≥146 U/L). Among patients who had low baseline BALP (n=123), 25-month survival was similar for both treatment groups. Although zoledronic acid reduced the risk of death in this subset by approximately 30% compared with pamidronate in the univariate and multivariate analyses, the between-group differences were not statistically significant (P>.2 for both). In contrast, among patients with high baseline BALP (n=89), zoledronic acid significantly improved survival compared with pamidronate (82% versus 53%; P=.041). Zoledronic acid significantly reduced the risk of death in this subset by approximately 56% compared with pamidronate in both the univariate and multivariate analyses (P<.05 for both). These exploratory analyses suggest that, in addition to its established benefits in preventing skeletal complications, zoledronic acid may improve survival compared with pamidronate in patients with multiple myeloma who have high BALP levels. Prospective trials are needed to investigate the improved survival in this subset; the high-BALP subset may have higher statistical power to distinguish between the 2 bisphosphonates (higher event rate), or these patients may still have coupled bone metabolism and better recovery after response to antiresorptive therapy.

Effect of the number of bone lesions on efficacy of zoledronic acid for prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8529-8529 ◽  
Author(s):  
N. Shirina ◽  
R. E. Coleman ◽  
Y. M. Chen
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Lung Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Solid Tumors ◽  
Morbidity Rate ◽  
Bone Lesions ◽  
The Mean

8529 Background: It has been postulated that greater numbers of bone metastases and thus greater tumor burden may lead to increased skeletal morbidity. To assess the effect that the number of baseline bone metastases may have on the efficacy of zoledronic acid in patients with solid tumors, we conducted a retrospective analysis of 3 large, randomized, controlled trials. Methods: Data were evaluated from the intent-to-treat population with breast cancer (n = 739), prostate cancer (n = 397), or lung cancer and other solid tumors (n = 480) who were treated with zoledronic acid 4 mg, pamidronate 90 mg, or placebo and had information available on number of baseline bone lesions. Patients were stratified into 2 groups: those with ≤ 3 bone lesions or > 3 lesions. Results: In general, patients with > 3 lesions had a higher skeletal morbidity rate (SMR) compared with patients with ≤ 3 lesions (Table 1), and zoledronic acid reduced SREs regardless of the number of bone lesions, but the benefit of zoledronic acid appeared greater in patients with > 3 lesions. In patients with lung cancer and other solid tumors who had > 3 bone lesions, zoledronic acid significantly reduced the mean SMR (P = .008) and significantly prolonged time to first SRE (median, 171 vs 84 day; P = .005) compared with placebo. In prostate cancer patients with > 3 bone lesions, zoledronic acid also significantly reduced the mean SMR compared with placebo (Table 1). In breast cancer patients with > 3 bone lesions, the mean SMRs were similar for zoledronic acid and pamidronate groups (Table 1). Conclusions: Patients with a greater number of bone lesions are at higher risk for skeletal complications and receive greater clinical benefit from treatment with zoledronic acid. [Table: see text] [Table: see text]

scholarly journals Role of Bone Targeting Agents in the Prevention of Bone Metastases from Breast Cancer

2020 ◽  
Vol 21 (8) ◽  
pp. 3022 ◽  
Author(s):  
Stella D’Oronzo ◽  
Erica Silvestris ◽  
Angelo Paradiso ◽  
Mauro Cives ◽  
Marco Tucci
Keyword(s):  
Breast Cancer ◽  
Bone Metastases ◽  
Bone Lesions ◽  
Bone Targeting ◽  
Incurable Condition ◽  
Skeletal Complications ◽  
Risk Patients

Breast cancer (BC) is the most common malignancy in women worldwide and leads, in more than 70% of patients with advanced disease, to skeleton colonization and formation of bone metastases (BM). This condition implies a severe disability and deterioration of the quality of life, with consequent additional social costs. In recent decades, several studies explored the role of agents acting within the bone microenvironment to counteract BM development, and several bone-targeting agents (BTAs) have been introduced in the clinical practice to manage bone lesions and reduce the risk of skeletal complications. However, long-term exposure to these agents is not free from potential toxicities and needs careful monitoring. In this context, the potential capability to prevent BM onset in selected BC patients, through the early administration of BTAs, has been explored by several researchers, with the belief that “prevention is better than cure” and that, ultimately, metastatic BC is an incurable condition. Here, we revised the mechanisms of BM development in BC as well as the strategies for selecting high-risk patients suitable for early BTA treatment.

scholarly journals Maxillary Bone Regeneration Based on Nanoreservoirs Functionalizedε-Polycaprolactone Biomembranes in a Mouse Model of Jaw Bone Lesion

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Marion Strub ◽  
Xavier Van Bellinghen ◽  
Florence Fioretti ◽  
Fabien Bornert ◽  
Nadia Benkirane-Jessel ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Tissue ◽  
Bone Lesion ◽  
Electrospun Nanofibers ◽  
Bone Lesions ◽  
Tissue Quality ◽  
Maxillary Bone ◽  
Bone Response ◽  
Skeletal Defects

Current approaches of regenerative therapies constitute strategies for bone tissue reparation and engineering, especially in the context of genetical diseases with skeletal defects. Bone regeneration using electrospun nanofibers’ implant has the following objectives: bone neoformation induction with rapid healing, reduced postoperative complications, and improvement of bone tissue quality.In vivoimplantation of polycaprolactone (PCL) biomembrane functionalized with BMP-2/Ibuprofen in mouse maxillary defects was followed by bone neoformation kinetics evaluation using microcomputed tomography. Wild-Type (WT) and Tabby (Ta) mice were used to compare effects on a normal phenotype and on a mutant model of ectodermal dysplasia (ED). After 21 days, no effect on bone neoformation was observed in Ta treated lesion (4% neoformation compared to 13% in the control lesion). Between the 21st and the 30th days, the use of biomembrane functionalized with BMP-2/Ibuprofen in maxillary bone lesions allowed a significant increase in bone neoformation peaks (resp., +8% in mutant Ta and +13% in WT). Histological analyses revealed a neoformed bone with regular trabecular structure, areas of mineralized bone inside the membrane, and an improved neovascularization in the treated lesion with bifunctionalized membrane. In conclusion, PCL functionalized biomembrane promoted bone neoformation, this effect being modulated by the Ta bone phenotype responsible for an alteration of bone response.

Musculoskeletal Manifestations of Sarcoidosis: A Review Article

2019 ◽  
Vol 15 (2) ◽  
pp. 83-89 ◽  
Author(s):  
Somayeh Shariatmaghani ◽  
Roshanak Salari ◽  
Maryam Sahebari ◽  
Payman Shalchian Tabrizi ◽  
Masoumeh Salari
Keyword(s):  
Treatment Options ◽  
Immunosuppressive Drugs ◽  
Bone Lesions ◽  
Symptomatic Management ◽  
Muscular Disease ◽  
Initial Symptoms ◽  
Skeletal Complications ◽  
Musculoskeletal Manifestations ◽  
Fdg Pet Ct ◽  
Musculoskeletal Involvement

Background: Sarcoidosis is a multisystem inflammatory disease with an etiology that is not clearly understood. Amongst the different organs that may be affected, the lungs are the most common. Musculoskeletal manifestations of the disease are uncommon. Objectives: They include arthropathy, bone lesions, or myopathy, all of which may occur as initial symptoms or develop during the course of the disease. Methods: : Articular involvement my present as arthralgia or arthritis. Skeletal complications usually develop in the chronic state of the disease. Muscular disease is rare and usually asymptomatic. Appropriate imaging modalities including X-ray, MRI, FDG-PET/CT assist in the diagnosis of rheumatic sarcoidosis. However, biopsy is necessary for definite diagnosis. Result and Conclusion: In most cases of musculoskeletal involvement, NSAIDs and corticosteroids are sufficient for symptomatic management. For more resistant cases immunosuppressive drugs (i.e., methotrexate) and TNF- inhibitors are used. Our aim is to review various types of musculoskeletal involvement in sarcoidosis and their existing treatment options.

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