Oral ibandronic acid versus intravenous zoledronic acid in treatment of bone metastases from breast cancer: a randomised, open label, non-inferiority phase 3 trial

Barrett-Lee, Peter; Casbard, Angela; Abraham, Jacinta; Hood, Kerenza; Coleman, Robert E.; Simmonds, Peter; Timmins, Hayley; Wheatley, Duncan; Grieve, Robert; Griffiths, Gareth; Murray, Nick

doi:10.1016/s1470-2045(13)70539-4

Cited by 113 publications

(96 citation statements)

References 10 publications

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“…Indeed, ZA has been shown to effectively reduce the risk of skeletal-related events in patients with metastatic PCa [20], multiple myeloma [21] and breast cancer [20,22,23]. ZA has also recently been tested as an additive therapeutic for earlystage breast cancer [24][25][26].…”

Section: Discussionmentioning

confidence: 99%

312: Zoledronic acid impairs stromal reactivity by inhibiting M2-macrophages polarization and prostate cancer-associated fibroblasts

Comito¹,

Segura²,

Sobierajska³

et al. 2014

European Journal of Cancer

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Zoledronic acid (ZA) is a biphosphonate used for osteoporosis treatment and also proved to be effective to reduce the pain induced by bone metastases when used as adjuvant therapy in solid cancers. However, it has been recently proposed that ZA could have direct anti-tumour effects, although the molecular mechanism is unknown. We herein unravel a novel anti-tumour activity of ZA in prostate cancer (PCa), by targeting the pro-tumorigenic properties of both stromal and immune cells. Particularly, we demonstrate that ZA impairs PCa-induced M2-macrophages polarization, reducing their pro-invasive effect on tumour cells and their pro-angiogenic features. Crucially, ZA administration reverts cancer associated fibroblasts (CAFs) activation by targeting the mevalonate pathway and RhoA geranyl-geranylation, thereby impairing smooth muscle actin-α fibers organization, a prerequisite of fibroblast activation. Moreover, ZA prevents the M2 macrophages-mediated activation of normal fibroblast, highlighting the broad efficacy of this drug on tumour microenvironment. These results are confirmed in a metastatic xenograft PCa mouse model in which ZA-induced stromal normalization impairs cancer-stromal cells crosstalk, resulting in a significant reduction of primary tumour growth and metastases. Overall these findings reinforce the efficacy of ZA as a potential therapeutic approach to reduce cancer aggressiveness, by abrogating the supportive role of tumour microenvironment.

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Section: Discussionmentioning

confidence: 99%

312: Zoledronic acid impairs stromal reactivity by inhibiting M2-macrophages polarization and prostate cancer-associated fibroblasts

Comito¹,

Segura²,

Sobierajska³

et al. 2014

European Journal of Cancer

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“…In a recent phase III trial (ZICE trial), oral ibandronate was inferior to infusional zoledronic acid in reducing SRE frequency. Both drugs had similar, acceptable side effect profile (Barrett-Lee et al, 2014). However oral administration of ibandronate can be advantageous for patients who do not want parenteral drugs.…”

Section: Efficacy Of Bisphosphonatesmentioning

confidence: 96%

Medical Treatment of Breast Cancer Bone Metastasis: From Bisphosphonates to Targeted Drugs

Erdoğan

Çiçin²

2014

Asian Pacific Journal of Cancer Prevention

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Breast cancer bone metastasis causing severe morbidity is commonly encountered in daily clinical practice. It causes pain, pathologic fractures, spinal cord and other nerve compression syndromes and life threatening hypercalcemia. Breast cancer metastasizes to bone through complicated steps in which numerous molecules play roles. Metastatic cells disrupt normal bone turnover and create a vicious cycle to which treatment efforts should be directed. Bisphosphonates have been used safely for more than two decades. As a group they delay time to first skeletal related event and reduce pain, but do not prevent development of bone metastasis in patients with no bone metastasis, and also do not prolong survival. The receptor activator for nuclear factor kB ligand inhibitor denosumab delays time to first skeletal related event and reduces the skeletal morbidity rate. Radionuclides are another treatment option for bone pain. New targeted therapies and radionuclides are still under investigation. In this review we will focus on mechanisms of bone metastasis and its medical treatment in breast cancer patients.

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“…Hortobagyi et al [3,27], Hultborn et al [29], and Kohno et al [34] did not sufficiently address incomplete outcome data. In the study by Conte et al [26], placebo infusions were not administered to control because ofethical objections in several countries, and the study by Barrett-Lee et al [35] had an openlabel design. Our searches were appropriate, but the possibility of publication bias cannot be excluded; however, it is unclear whether reporting biases would tend to favor any particular treatment.…”

Section: Study Qualitymentioning

confidence: 99%

Systematic Literature Review and Network Meta-Analysis Comparing Bone-Targeted Agents for the Prevention of Skeletal-Related Events in Cancer Patients With Bone Metastasis

Wang

Qiao

et al. 2015

The Oncologist

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Oral ibandronic acid versus intravenous zoledronic acid in treatment of bone metastases from breast cancer: a randomised, open label, non-inferiority phase 3 trial

Cited by 113 publications

References 10 publications

312: Zoledronic acid impairs stromal reactivity by inhibiting M2-macrophages polarization and prostate cancer-associated fibroblasts

312: Zoledronic acid impairs stromal reactivity by inhibiting M2-macrophages polarization and prostate cancer-associated fibroblasts

Medical Treatment of Breast Cancer Bone Metastasis: From Bisphosphonates to Targeted Drugs

Systematic Literature Review and Network Meta-Analysis Comparing Bone-Targeted Agents for the Prevention of Skeletal-Related Events in Cancer Patients With Bone Metastasis

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