Long-term safety of monthly zoledronic acid therapy beyond 1 year in patients with advanced cancer involving bone (LoTESS): A multicentre prospective phase 4 study

Khalafallah, Alhossain A; Slancar, Michael; Cosolo, W; Abdi, Ehtesham; Chern, Boris; Woodfield, RJ; Copeman, Michael

doi:10.1111/ecc.12638

Cited by 5 publications

(3 citation statements)

References 26 publications

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“…However, in patients with locally advanced breast cancer, ZOL combined with neoadjuvant chemotherapy had no significant effect on clinical outcomes in the overall cohort and, surprisingly, was also associated with increased extraosseous recurrence and shorter survival in patients with ER+/HER2- cancer who were less than 45 years of age [ 165 ]. The benefits of continuous monthly use of ZOL for at least 2 years outweighed the risks in patients with advanced bone tumors, including those related to breast cancer, prostate cancer, and multiple myeloma, according to follow-up studies [ 177 ]. In the palliative care setting, continuous second-line zoledronic acid treatment can significantly relieve pain, reduce the n-telopeptide (NTX) level, and exert a relevant palliative care effect on breast cancer patients with bone-related event or progressive bone metastases, after previous first-line bisphosphonate treatment [ 178 ].…”

Section: Therapies For Bone Metastasismentioning

confidence: 99%

Bone Metastasis of Breast Cancer: Molecular Mechanisms and Therapeutic Strategies

Pang

Gan

et al. 2022

Cancers

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Bone metastasis is a common complication of many types of advanced cancer, including breast cancer. Bone metastasis may cause severe pain, fractures, and hypercalcemia, rendering clinical management challenging and substantially reducing the quality of life and overall survival (OS) time of breast cancer patients. Studies have revealed that bone metastasis is related to interactions between tumor cells and the bone microenvironment, and involves complex molecular biological mechanisms, including colonization, osteolytic destruction, and an immunosuppressive bone microenvironment. Agents inhibiting bone metastasis (such as bisphosphate and denosumab) alleviate bone destruction and improve the quality of life of breast cancer patients with bone metastasis. However, the prognosis of these patients remains poor, and the specific biological mechanism of bone metastasis is incompletely understood. Additional basic and clinical studies are urgently needed, to further explore the mechanism of bone metastasis and develop new therapeutic drugs. This review presents a summary of the molecular mechanisms and therapeutic strategies of bone metastasis of breast cancer, aiming to improve the quality of life and prognosis of breast cancer patients and provide a reference for future research directions.

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Section: Therapies For Bone Metastasismentioning

confidence: 99%

Bone Metastasis of Breast Cancer: Molecular Mechanisms and Therapeutic Strategies

Pang

Gan

et al. 2022

Cancers

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“…In PCa skeletal metastasis animal models, we and others have demonstrated anti-resorptive agents such as soluble receptor activator of NF-kappaB (sRANK) (Zhang et al 2003), osteoprotegerin (OPG) (Zhang et al 2001), and overexpression of OPG successfully diminished the tumor growth in bone (Corey et al 2005). In clinical application, ZA effectively reduces metastasis-related bone pain and skeletal complications in patients with metastatic PCa and breast cancer (Saad et al 2004), whereas more than 30% of patients will experience at least one skeletal complication after ZA therapy within a 2-year period, and ZA-unrelated serious events (Khalafallah et al 2018; Rosen et al 2004). Therefore, new effective treatments are urgently needed for patients with bone metastases and those at high risk of developing bone metastases.…”

Section: Introductionmentioning

confidence: 99%

Targeting cathepsin K diminishes prostate cancer establishment and growth in murine bone

Liang

Wang

Chen

et al. 2019

J Cancer Res Clin Oncol

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Background The processes of prostate cancer (PCa) invasion and metastasis are facilitated by proteolytic cascade involving multiple proteases, such as matrix metalloproteinases, serine proteases and cysteine proteases including cathepsin K (CatK). CatK is predominantly secreted by osteoclasts and specifically degrades collagen I leading to bone destruction. PCa and breast cancer preferentially metastasize to the bone. Importantly, CatK expression level is greater in PCa bone metastatic sites compared to primary tumor and normal prostate tissues. However, the underlying mechanism of CatK during PCa metastases into the bone remains to be elucidated. We investigated the functional role of CatK during the PCa establishment and growth process in the murine bone. Methods CatK mRNA expression was validated by RT-PCR, protein expression by immunoblotting in PCa LNCaP, C4-2B, and PC3 cells as well as in PCa tissues. Its protein production was measured using ELISA assay. The effect of both knockdowns via siRNA and CatK inhibitor was compared in regard to PCa cell invasion. We further studied the dose-dependent CatK inhibitor effect on conditioned media-induced bone resorption. In setting up an animal model, C4-2B cells were injected into the tibiae of SCID mice. The animals treated with either vehicle or CatK inhibitor for 8 weeks at the time of tumor cell injection (tumor establishment model; protocol I) or 4 weeks after tumor cell injection (tumor progression model; protocol II) were applied to histological and histomorphometric analyses. Results We confirmed CatK expression in PCa LNCaP, C4-2B, and PC3 cells as well as in PCa tissues. Furthermore, we observed the inhibitory effects of a selective CatK inhibitor on PCa cell invasion. The CatK inhibitor dose-dependently inhibited PCa-conditioned media-induced bone resorption. Upon injection of C4-2B cells into the tibiae of SCID mice, the selective CatK inhibitor significantly prevented the tumor establishment in protocol I, and reduced the tumor growth in bone in protocol II. It also decreased serum PSA levels in both animal models. The inhibitory effects of the CatK inhibitor were enhanced in combination with zoledronic acid (ZA). Conclusion The selective CatK inhibitor may prevent the establishment and progression of PCa in bone, thus making it a novel therapeutic approach for advanced PCa.

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“…Strontium-89 and bisphosphonates can also effectively alleviate bone pain. 2 Pain resulting from bone-destructive erosion, periosteal expansion under tension, or structural/mechanical instability may be managed with percutaneous cementoplasty techniques such as vertebroplasty, kyphoplasty, or osteoplasty. An epidural and intrathecal drug infusion system may also be deployed.…”

Section: Introductionmentioning

confidence: 99%

Integrated approach to pain management for a patient with multiple bone metastases of uterine cervical cancer

Qin

Song

et al. 2018

J Int Med Res

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BackgroundPain management for multiple bone metastases is complex and often requires multidisciplinary treatment. We herein describe patient-centered multidisciplinary pain management for metastatic cancer.Case presentation: A 61-year-old woman with multiple bone metastases of uterine cervical cancer developed intractable low back pain. After external beam radiotherapy failed, we performed lumbar spinal intralesional curettage, pedicle screw fixation, and nerve decompression. However, the neuralgia persisted. We then percutaneously injected epirubicin into the intervertebral foramina under computed tomography guidance for L5 dorsal root ganglion destruction. Osteoplasty was performed under C-arm X-ray guidance; however, the sacrum was mistaken for the ilium, and treatment was ineffective. We administered zoledronic acid and strontium-89. The last resort was outpatient implantation of an epidural bupivacaine-morphine infusion system. A visual analog scale (VAS) was used for pain evaluation. Lumbar spinal intralesional curettage and fixation, epirubicin-induced ganglion destruction, and administration of zoledronic acid and strontium-89 decreased her VAS pain score from 7–8 to 3–4. Radiotherapy and nerve decompression and release were ineffective, as was osteoplasty because of the location error. The epidural infusion system decreased the VAS score from 7–8 to 2–3 and was highly efficient.ConclusionsMultidisciplinary integrated treatment for metastatic cancer can be effective.

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Long-term safety of monthly zoledronic acid therapy beyond 1 year in patients with advanced cancer involving bone (LoTESS): A multicentre prospective phase 4 study

Cited by 5 publications

References 26 publications

Bone Metastasis of Breast Cancer: Molecular Mechanisms and Therapeutic Strategies

Bone Metastasis of Breast Cancer: Molecular Mechanisms and Therapeutic Strategies

Targeting cathepsin K diminishes prostate cancer establishment and growth in murine bone

Integrated approach to pain management for a patient with multiple bone metastases of uterine cervical cancer

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