Phase II Trial Evaluating the Palliative Benefit of Second-Line Zoledronic Acid in Breast Cancer Patients With Either a Skeletal-Related Event or Progressive Bone Metastases Despite First-Line Bisphosphonate Therapy

Clemons, Mark; Dranitsaris, George; Ooi, Wei; Yogendran, Geetha; Sukovic, Tatjana; Wong, Betty; Verma, Sunil; Pritchard, Kathleen I.; Trudeau, Maureen; Cole, David E. C.

doi:10.1200/jco.2006.05.9212

Cited by 129 publications

(98 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Because patients with bone-only metastatic disease may survive several years, and the risk of adverse events from bisphosphonates increases with cumulative exposure, several ongoing trials are exploring the possibility that more infrequent bisphosphonate doses may be as effective as standard doses 47,48 . In addition, small phase ii trials have explored the strategy of switching to novel or more potent agents for patients at high risk of further sres on a bisphosphonate 49,50 . In one of those trials 49 , 31 patients who experienced either a sre or progressive bone metastases while receiving clodronate or pamidronate were switched to zoledronate, a more potent bisphosphonate; after 8 weeks, pain control had improved significantly.…”

Section: Discussionmentioning

confidence: 99%

Bone-Targeted Agents and Skeletal-Related Events in Breast Cancer Patients with Bone Metastases: The State of the Art

et al. 2012

View full text Add to dashboard Cite

Most women with advanced breast cancer will develop bone metastases, which are associated with the development of skeletal-related events (sres) such as pathologic fractures and spinal cord compression. This article reviews the evolving definition and incidence of sres, the pathophysiology of bone metastases, and the key evidence for the safety and efficacy of the currently available systemic treatment options for preventing and delaying sres in the setting of breast cancer with bone metastases. The bisphosphonates are structural analogues of endogenous pyrophosphate; three of them (clodronate, pamidronate, and zoledronate) are currently approved for use in Canada in the setting of breast cancer with bone metastases. Denosumab is a fully human immunoglobulin G2 monoclonal antibody that binds to human rankl (receptor activator of nuclear factor κB ligand), thereby preventing osteoclast formation, function, and survival, and reducing cancer-induced destruction of bone. Denosumab has recently been approved in Canada for reducing the risk of sres from the bone metastases associated with a variety of malignancies, including breast cancer. How to predict the patients that will benefit most from prophylactic treatment, the agents to select and the timing of switches between agents, the dosing schedules and durations of treatment to choose, the potential utility of the agents in the adjuvant setting, and the utility of additional endpoints such as markers of bone resorption are among the outstanding questions with respect to the optimal use of antiresorptive agents for patients with breast cancer and bone metastases.

show abstract

Section: Discussionmentioning

confidence: 99%

Bone-Targeted Agents and Skeletal-Related Events in Breast Cancer Patients with Bone Metastases: The State of the Art

et al. 2012

View full text Add to dashboard Cite

show abstract

“…11 Urinary NTx levels are indeed increased in patients with solid tumors and BM, and usually decrease after bisphosphonate therapy. 11,12 Interestingly, patients in whom urinary NTx levels do not decrease after initial bisphosphonate therapy may be at higher risk of skeletal adverse events such as pathological fractures, and may be candidates for a switch to more potent bisphosphonates. 12 NTx can also be measured in serum, as a biochemical marker of bone resorption, with similar results to those obtained with urinary NTx.…”

Section: Introductionmentioning

confidence: 99%

“…11,12 Interestingly, patients in whom urinary NTx levels do not decrease after initial bisphosphonate therapy may be at higher risk of skeletal adverse events such as pathological fractures, and may be candidates for a switch to more potent bisphosphonates. 12 NTx can also be measured in serum, as a biochemical marker of bone resorption, with similar results to those obtained with urinary NTx. 7,13 NTx assays in serum may be more convenient than urine assays, since blood can be drawn simultaneously for all other routine biochemical and hematological tests.…”

Section: Introductionmentioning

confidence: 99%

Serum cross-linked n-telopeptides of type 1 collagen (NTx) in patients with solid tumors

et al. 2009

View full text Add to dashboard Cite

CONTEXT AND OBJECTIVE: Cross-linked N-telopeptides of type I collagen (NTx) increase in concentration in situations in which bone resorption is increased, such as osteoporosis and bone metastasis (BM). We aimed to evaluate the serum concentrations of NTx in a sample of patients with several types of solid tumors. DESIGN AND SETTING:Cross-sectional analytical study with a control group in a tertiary public hospital. METHODS:We performed the quantitative enzyme-linked immunosorbent assay (ELISA) on serum NTx levels in 19 subjects without a history of cancer and 62 patients with various solid tumors who had been referred for a bone scan. Three experienced analysts read all bone scans. RESULTS:The serum NTx levels in patients with cancer and BM, with cancer but without BM and without cancer were 46.77 ± 2.58, 32.85 ± 2.05 and 22.32 ± 2.90 respectively (P < 0.0001). We did not find any significant correlations of serum NTx with age, gender, history of bone pain, tumor type and bone alkaline phosphatase levels. We found a significant correlation between serum NTx and alkaline phosphatase levels (R 2 = 0.08; P = 0.022).CONCLUSIONS: Serum NTx levels are significantly higher in patients with solid tumors and bone metastases than they are in patients without bone metastases and in normal controls.RESUMO CONTEXTO E OBJETIVO: Os N-telopeptídeos do colágeno tipo-I (NTx) elevam-se quando a reabsorção óssea está aumentada, devido a condições como osteoporose e metástase óssea. Sendo assim, temos por objetivo avaliar os níveis séricos de NTx em uma população heterogênea de pacientes com tumores sólidos. TIPO DE ESTUDO E LOCAL:Estudo transversal analítico com grupo controle, realizado em hospital público terciário.MÉTODOS: 19 pacientes sem história de câncer e 62 pacientes com tumores sólidos de vários tipos, encaminhados para estadiamento e investigação dos sintomas esqueléticos, foram avaliados pela técnica de ELISA (Enzyme Linked Immuno Sorbent Assay) quantitativa para a dosagem de NTx. Três especialistas leram todas as imagens ósseas.RESULTADOS: O nível de NTx encontrado em pacientes com câncer e metástase óssea, sem metástase óssea e sem diagnóstico de câncer foi 46,77 ± 2,58, 32,85 ± 2,05 e 22,32 ± 2,90, respectivamente (P < 0,0001). Não encontramos correlação entre o NTx, idade, sexo, história de dor óssea, tipo de tumor e níveis de fosfatase alcalina óssea. Encontramos correlação significativa entre os níveis de NTx e de Fosfatase Alcalina (r² = 0,08, P = 0,022).CONCLUSÃO: O NTx sérico é significativamente mais elevado em pacientes com tumores sólidos e metástases ósseas quando comparado com pacientes sem metástases ósseas e controles normais.

show abstract

“…Bisphosphonates can potently reduce telopeptide levels, 32,33 which correlate well with reduced pain. 34,35 Patients in this study had already been treated with bisphosphonates for a mean duration of 15.2 months and it is possible that these patients had therefore already experienced the maximal suppression of their bone turnover. If suppression was maximal, then neither telopeptide levels nor pain scores would be expected to change as a result of a high dose of vitamin D. It should be emphasized that patients in this study were administered different bisphosphonates, and these were given both orally and intravenously.…”

Section: Discussionmentioning

confidence: 99%

A phase 2 trial exploring the effects of high‐dose (10,000 IU/day) vitamin D₃ in breast cancer patients with bone metastases

Amir

Simmons

Freedman

et al. 2009

Cancer

Self Cite

View full text Add to dashboard Cite

BACKGROUND: Vitamin D deficiency has potential roles in breast cancer etiology and progression. Vitamin D deficiency has also been associated with increased toxicity from bisphosphonate therapy. The optimal dose of vitamin D supplementation is unknown, but daily sunlight exposure can generate the equivalent of a 10,000-IU oral dose of vitamin D 3 . This study therefore aimed to assess the effect of this dose of vitamin D 3 in patients with bone metastases from breast cancer. METHODS: Patients with bone metastases treated with bisphosphonates were enrolled into this single-arm phase 2 study. Patients received 10,000 IU of vitamin D 3 and 1000 mg of calcium supplementation each day for 4 months. The effect of this treatment on palliation, bone resorption markers, calcium metabolism, and toxicity were evaluated at baseline and monthly thereafter. RESULTS: Forty patients were enrolled. No significant changes in bone resorption markers were seen. Despite no change in global pain scales, there was a significant reduction in the number of sites of pain. A small but statistically significant increase in serum calcium was seen, as was a significant decrease in serum parathyroid hormone. Treatment unmasked 2 cases of primary hyperparathyroidism, but was not associated with direct toxicity. CONCLUSIONS: Daily doses of 10,000 IU vitamin D 3 for 4 months appear safe in patients without comorbid conditions causing hypersensitivity to vitamin D. Treatment reduced inappropriately elevated parathyroid hormone levels, presumably caused by long-term bisphosphonate use. There did not appear to be a significant palliative benefit nor any significant change in bone resorption. Cancer 2010;116:284-91.

show abstract

Phase II Trial Evaluating the Palliative Benefit of Second-Line Zoledronic Acid in Breast Cancer Patients With Either a Skeletal-Related Event or Progressive Bone Metastases Despite First-Line Bisphosphonate Therapy

Cited by 129 publications

References 22 publications

Bone-Targeted Agents and Skeletal-Related Events in Breast Cancer Patients with Bone Metastases: The State of the Art

Bone-Targeted Agents and Skeletal-Related Events in Breast Cancer Patients with Bone Metastases: The State of the Art

Serum cross-linked n-telopeptides of type 1 collagen (NTx) in patients with solid tumors

A phase 2 trial exploring the effects of high‐dose (10,000 IU/day) vitamin D₃ in breast cancer patients with bone metastases

Contact Info

Product

Resources

About

Phase II Trial Evaluating the Palliative Benefit of Second-Line Zoledronic Acid in Breast Cancer Patients With Either a Skeletal-Related Event or Progressive Bone Metastases Despite First-Line Bisphosphonate Therapy

Cited by 129 publications

References 22 publications

Bone-Targeted Agents and Skeletal-Related Events in Breast Cancer Patients with Bone Metastases: The State of the Art

Bone-Targeted Agents and Skeletal-Related Events in Breast Cancer Patients with Bone Metastases: The State of the Art

Serum cross-linked n-telopeptides of type 1 collagen (NTx) in patients with solid tumors

A phase 2 trial exploring the effects of high‐dose (10,000 IU/day) vitamin D3 in breast cancer patients with bone metastases

Contact Info

Product

Resources

About

A phase 2 trial exploring the effects of high‐dose (10,000 IU/day) vitamin D₃ in breast cancer patients with bone metastases