New results from the use of bisphosphonates in cancer patients

Coleman, Robert E.; Gnant, Michael

doi:10.1097/spc.0b013e32832f4149

Cited by 23 publications

(10 citation statements)

References 55 publications

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“…Notably, zoledronic acid appeared to reduce distant recurrence at bone sites (16 vs. 23 events) and other distant sites (all distant recurrences: 29 vs. 41 events), as well as locoregional recurrences (10 vs. 20 events) compared to no zoledronic acid [52]. This suggests that the anticancer activity of zoledronic acid may be related in part to its effects on the tumor microenvironment in the bone marrow (the ‘soil’), which can serve as a source of dormant tumor stem cells, and also to its effects on DTCs (the ‘seed’), as noted earlier [55,67]. Several questions remain to be elucidated from these results, including the reason for the delay in the DFS effect, which emerged following the completion of zoledronic acid treatment.…”

Section: Clinical Trials Of Zoledronic Acid: Anticancer Propertiesmentioning

confidence: 83%

“…DTCs) as well as the ‘soil’ (i.e. the tumor microenvironment) [61,63,66,67]. Recent results from the ZO-FAST trial (see below) provide further evidence for fewer metastases with zoledronic acid in combination with letrozole [50].…”

Section: Beyond Reducing Aibl: Anticancer Effects Of Bisphosphonatesmentioning

confidence: 99%

“…This could be due in part to limited potency and/or bioavailability of oral bisphosphonates [55]. The anticancer effects of bisphosphonates appear to be proportional to their potency in terms of antiresorptive capacity [67]. Because zoledronic acid is one of the most active approved bisphosphonates for use in clinical practice [40], further discussion of the anticancer properties of bisphosphonates is limited to clinical studies with zoledronic acid.…”

Section: Beyond Reducing Aibl: Anticancer Effects Of Bisphosphonatesmentioning

confidence: 99%

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Women and Bone Health: Maximizing the Benefits of Aromatase Inhibitor Therapy

Tang¹

2010

Oncology

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Postmenopausal women with early breast cancer (EBC) are already at risk for bone loss, osteoporosis and fracture as they age because of declining estrogen levels. Adjuvant hormonal therapy with aromatase inhibitors (AIs; e.g. letrozole, anastrozole, exemestane) can exacerbate this risk. All three AIs appear to have similar effects on bone, increasing bone turnover and fracture risk in postmenopausal women with EBC. Risk factors for bone loss can be used to assess fracture risk and the need for ongoing assessment and/or treatment in postmenopausal women receiving AIs for EBC. The concomitant, up-front use of intravenous bisphosphonate therapy, such as zoledronic acid, in combination with AIs can inhibit bone loss. In addition, a strong body of evidence suggests an anticancer activity of bisphosphonate therapy with zoledronic acid in EBC in both the pre- and postmenopausal adjuvant setting. Zoledronic acid thus provides a therapeutic option for postmenopausal women with EBC who may be at higher risk for bone loss while on AIs, allowing more patients to receive treatment with effective adjuvant hormonal therapy to prevent recurrence.

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Section: Clinical Trials Of Zoledronic Acid: Anticancer Propertiesmentioning

confidence: 83%

Section: Beyond Reducing Aibl: Anticancer Effects Of Bisphosphonatesmentioning

confidence: 99%

Section: Beyond Reducing Aibl: Anticancer Effects Of Bisphosphonatesmentioning

confidence: 99%

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Women and Bone Health: Maximizing the Benefits of Aromatase Inhibitor Therapy

Tang¹

2010

Oncology

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“…However, discovering new uses for the old drugs may accelerate the development and application of new therapies, take for example, the bisphosphonate zoledronic acid can decrease breast cancer metastasis beside treatment of osteoporosis and similar diseases (Coleman and Gnant, 2009) and thalidomide can treat multiple myeloma in addition to alleviate nausea and morning sickness (Cavo et al, 2009). Importantly, protective effect of some local and gerenral anesthetics and sedatives have reported against infection, and inflammations (Plachinta et al, 2003;Gallos et al, 2004;Fuentes et al, 2006;de Klaver et al, 2002;Liu et al, 2009) are likely to yield new insights into anti-inflammatory therapies.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of 2,2,2-trichloroethanol on peptidoglycan-induced inflammation in murine macrophages

Ye¹,

Li²,

Wang³

et al. 2014

Afr. J. Pharm. Pharmacol.

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The aim of this study was to investigate the effect of 2,2,2-trichloroethanol on peptidoglycan-induced murine macrophages inflammation. The effect of 2,2,2-trichloroethanol on the production of TNF-α and IL-6 by murine peritoneal macrophages with peptidoglycan-stimulation were investigated. Also, RAW264.7 macrophages transfected with a NF-κB luciferase reporter plasmid with the stimulation of peptidoglycan were used to test the effect of 2,2,2-trichloroethanol on NF-κB activity. Flow cytometry and Western blotting were used to check the expression levels of toll-like receptor 2 on treated RAW264.7 macrophages. 2,2,2-Trichloroethanol decreased the unregulated levels of IL-6 and TNF-α produced by the peritoneal macrophages stimulation with peptidoglycan. The NF-κB activities of the RAW264.7 macrophages stimulated by peptidoglycan were decreased. 2,2,2-Trichloroethanol decreased the peptidoglycan-induced murine macrophage inflammation response.

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“…[74][75][76] In addition to their primary effect upon bone mineral density, bisphosphonates also may confer additional anticancer benefits. Several direct and indirect mechanisms may contribute to this anticancer activity, including cancer cell apoptosis, inhibition of proliferation and migration, reduction in angiogenesis, activation of the immune system against cancer cells, and synergistic effects with other cancer treatments such as endocrine and chemotherapies.…”

Section: Potential Anticancer Activity Of Bisphosphonatesmentioning

confidence: 99%

Aromatase inhibitor-associated bone loss and its management with bisphosphonates in patients with breast cancer

Bauer

Bryce²,

Hadji

2012

BCTT

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Abstract:Postmenopausal women have an increased risk of osteopenia and osteoporosis due to loss of the bone-protective effects of estrogen. Disease-related processes may also contribute to the risk of bone loss in postmenopausal women with breast cancer. One of the most common and severe safety issues associated with cancer therapy for patients with breast cancer is bone loss and the associated increase in risk of fractures. This paper reviews the recent literature pertaining to aromatase inhibitor (AI)-associated bone loss, and discusses suggested management and preventative approaches that may help patients remain on therapy to derive maximum clinical benefit. A case study is presented to illustrate the discussion. We observed that AIs are in widespread use for women with hormone receptor-positive breast cancer and are now recommended as adjuvant therapy, either as primary therapy or sequential to tamoxifen, for postmenopausal women. AIs target the estrogen biosynthetic pathway and deprive tumor cells of the growth-promoting effects of estrogen, and AI therapies provide benefits to patients in terms of improved disease-free survival. However, there is a concern regarding the increased risk of bone loss with prolonged AI therapy, which can be managed in many cases with the use of bisphosphonates and other interventions (eg, calcium, vitamin D supplementation, exercise).

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New results from the use of bisphosphonates in cancer patients

Abstract: The roles of bisphosphonates in metastatic bone disease and the prevention of cancer treatment induced bone loss have been defined. However, results from ongoing metastasis prevention trials are required before routine adjuvant bisphosphonates can be recommended.

Cited by 23 publications

References 55 publications

Women and Bone Health: Maximizing the Benefits of Aromatase Inhibitor Therapy

Women and Bone Health: Maximizing the Benefits of Aromatase Inhibitor Therapy

Protective effect of 2,2,2-trichloroethanol on peptidoglycan-induced inflammation in murine macrophages

Aromatase inhibitor-associated bone loss and its management with bisphosphonates in patients with breast cancer

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