Efficacy of Pamidronate in Breast Cancer with Bone Metastases: A Randomized Double-Blind Placebo Controlled Multicenter Study

Hultborn, Ragnar; Gundersen, S.; Rydén, Stefan; Holmberg, E; Carstensen, John; Wallgren, U-B.; Kilany, Suzanne

doi:10.3109/02841869609083974

Cited by 60 publications

(49 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results were confirmed in a study reported by Hultborn et al [31]. Among 404 women with skeletal metastases from breast cancer, patients who were administered 60 mg of pamidronate i.v.…”

Section: Pamidronatesupporting

confidence: 81%

See 1 more Smart Citation

Bisphosphonates: Clinical Experience

2004

View full text Add to dashboard Cite

Bone is a preferred site of metastasis for many solid tumors, and the complications associated with bone metastases can result in significant skeletal morbidity including severe bone pain, pathologic fracture, spinal cord compression, and hypercalcemia of malignancy (HCM). Bisphosphonates are the current standard of care for preventing skeletal complications associated with bone metastases. Clinical trials investigating the benefit of bisphosphonate therapy have used a composite end point defined as a skeletalrelated event (SRE) or bone event, which typically includes pathologic fracture, spinal cord compression, radiation or surgery to bone, and HCM. Bisphosphonates have been shown to significantly reduce the incidence of these events in patients with bone metastases. 2004;9(suppl 4):14-27

show abstract

Section: Pamidronatesupporting

confidence: 81%

“…SREs were not assessed in that study. It is important to note that both the Hultborn et al [31] and Conte et al [32] studies did not evaluate the currently recommended dose of 90 mg pamidronate.…”

Section: Coleman 19mentioning

confidence: 99%

Bisphosphonates: Clinical Experience

2004

View full text Add to dashboard Cite

show abstract

“…Randomized trials in breast cancer patients have shown that bisphosphonate therapy in combination with either endocrine therapy or chemotherapy can significantly delay the onset of SREs and also reduce their frequency (25,(30)(31)(32)(33)(34). Moreover, in vitro studies have demonstrated that even though an increase in osteoclastic activity is considered to be the predominant mechanism for bone destruction, breast cancer deposits can directly resorb bone (17).…”

Section: Discussionmentioning

confidence: 99%

Examination of the mechanisms of osteolysis in patients with metastatic breast cancer

Clemons¹

2009

Oncol Rep

View full text Add to dashboard Cite

Abstract. The benefits of bisphosphonates (BPs) in reducing skeletal-related events (SREs) in patients with bone metastases has mainly been attributed to their potent osteoclast inhibiting effect. However, despite the use of modern systemic anticancer therapy including potent BPs, many patients with bone metastases continue to have SREs. An improved understanding of the fundamental mechanisms of bone destruction allows for further development of appropriate targeted treatments. In this study, archival paraffin-embedded bone metastases specimens from patients with metastatic breast cancer were examined for the presence of osteoclasts, expression of the receptor activator of nuclear factor κB (RANK), RANK Ligand (RANKL), osteoprotegerin (OPG) and vascular endothelial growth factor (VEGF). Histological specimens were available for primary breast cancer, lymph node metastases, normal breast and normal bone tissues for comparison. Bone metastasis specimens were available for 20 BP naïve patients and two BP-treated patients. Osteoclasts were significantly increased in the bone metastases of the BP naïve group compared to normal bone. No osteoclasts were detected in the BP-treated group. RANKL was predominantly expressed in osteoblasts and in the stromal elements of metastatic tissue. Conversely, RANK was present in osteoclasts of bone metastases and normal bone, as well as in tumor cells of metastatic lymph nodes and bone metastases. VEGF was strongly expressed in the control bone and bone metastases regardless of BP treatment. In summary, osteoclasts may not be the singular obligatory factor for osteolysis in bone metastases. An increased expression of RANKL in stromal tissue surrounding bone metastases, RANK in osteoclasts and VEGF may serve as future targeted therapies possibly in conjunction with bisphosphonates. The mechanisms for osteoclast expression and the expression of RANKL, RANK, OPG and VEGF merit further prospective analysis, particularly in the context of BP treatment and progressive bone metastases. IntroductionBreast cancer continues to be the most commonly diagnosed cancer in women in the developed world (1). Bone metastases are the most common site of metastatic recurrence (2) and are a major cause of morbidity for patients. Complications resulting from bone metastases include pain, reduced mobility and a reduced quality of life. In addition, patients are at a considerable risk of, so-called skeletal related events (SREs) such as the requirement for surgery and/or radiotherapy, pathological fractures, spinal cord compression and hypercalcaemia (3). Characteristically, patients with bone as the predominant site of metastatic spread tend to have a protracted disease course when compared to those patients with visceral metastases (4). Furthermore, patients with the disease confined to the skeleton have been found to be most likely to develop skeletal-related complications and hence derive the most benefit from treatment with bone-specific therapies (5).Bone resorption is dependent on a cytokine known a...

show abstract

“…Indeed, four placebo-controlled trials (n ϭ 1,453) concluded that i.v. pamidronate (45-90 mg 3-4 weekly) results in a significantly longer time (12.7 versus 7.0 months; p Ͻ .001) to the occurrence of the first SRE (HR, 0.77; 95% CI, 0.69 -0.87), lower incidence of SREs (53% versus 68%; p Ͻ .001), and longer time to progression of bone lesions (8.3 versus 5.6 months; p ϭ .02) [21,[23][24][25][26][27]. Moreover, evidence from a head-to-head comparison suggests its superiority over clodronate in both controlling symptoms and suppressing bone resorption [28].…”

Section: Breast Cancermentioning

confidence: 99%

Bisphosphonates in Oncology: Rising Stars or Fallen Heroes

Wyngaert

Huizing²,

Fossion

et al. 2009

The Oncologist

View full text Add to dashboard Cite

The introduction of bisphosphonates in oncology has dramatically changed the management of patients with metastatic bone disease. In this manuscript, we thoroughly scrutinize the available body of clinical trials supporting the use of bisphosphonates in this setting and review new and ongoing research. Additionally, we summarize the data showing the benefits of bisphosphonate use in the prevention of treatment-induced bone loss and the intriguing emerging evidence on the antitumor potential of some of these agents when used in the adjuvant setting. Finally, we address the need for a careful consideration of potential benefits of bisphosphonate therapy and the risk for osteonecrosis of the jaw, a recently recognized late-toxicity of their use. The Oncologist 2009;14:181-191

show abstract

Efficacy of Pamidronate in Breast Cancer with Bone Metastases: A Randomized Double-Blind Placebo Controlled Multicenter Study

Cited by 60 publications

References 4 publications

Bisphosphonates: Clinical Experience

Bisphosphonates: Clinical Experience

Examination of the mechanisms of osteolysis in patients with metastatic breast cancer

Bisphosphonates in Oncology: Rising Stars or Fallen Heroes

Contact Info

Product

Resources

About