Source: OAI


Les bisphosphonates (BPs) sont des outils thérapeutiques de choix pour le traitement de l'ostéolyse maligne. Toutefois, ils n’ont pas d’effet anti-tumoral et n’améliorent pas la survie des patients. C’est pourquoi nous avons testé leur efficacité en association avec de nouveaux agents pharmacologiques ciblant les cellules responsables de la résorption osseuse, les ostéoclastes.
Nous avons ainsi démontré qu’un inhibiteur de cathepsine K (CKI) réduit l’activité des ostéoclastes in vitro, et de ce fait, le développement des métastases osseuses in vivo en agissant indirectement sur les cellules tumorales. De plus, un inhibiteur de tyrosine kinase (Imatinib) ralentit la formation et la progression des métastases osseuses in vivo, en ayant une activité anti-ostéoclastique et anti-tumorale. Toutefois, bien qu’une polythérapie puisse favoriser une synergie d’action entre les médicaments, nos résultats montrent que dans nos conditions d’utilisation, aucune synergie significative entre le CKI, l’Imatinib et le BP zolédronate n’a lieu.

50 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine clinical practice guidelines for the use of bisphosphonates in the prevention and treatment of bone metastases in breast cancer and their role relative to other therapies for this condition. An expert multidisciplinary panel reviewed pertinent information from the published literature and meeting abstracts through May 1999. Additional data collected as part of randomized trials and submitted to the United States Food and Drug Administration were also reviewed, and investigators were contacted for more recent information. Values for levels of evidence and grade of recommendation were assigned by expert reviewers and approved by the panel. Expert consensus was used if there were insufficient published data. The panel addressed which patients to treat and when in their course of disease, specific drug delivery issues, duration of therapy, management of bony metastases with other therapies, and the public policy implications. The guideline underwent external review by selected physicians, members of the American Society of Clinical Oncology (ASCO) Health Services Research Committee, and the ASCO Board of Directors. Bisphosphonates have not had an impact on the most reliable cancer end point: overall survival. The benefits have been reductions in skeletal complications, ie, pathologic fractures, surgery for fracture or impending fracture, radiation, spinal cord compression, and hypercalcemia. Intravenous (IV) pamidronate 90 mg delivered over 1 to 2 hours every 3 to 4 weeks is recommended in patients with metastatic breast cancer who have imaging evidence of lytic destruction of bone and who are concurrently receiving systemic therapy with hormonal therapy or chemotherapy. For women with only an abnormal bone scan but without bony destruction by imaging studies or localized pain, there is insufficient evidence to suggest starting bisphosphonates. Starting bisphosphonates in patients without evidence of bony metastasis, even in the presence of other extraskeletal metastases, is not recommended. Studies of bisphosphonates in the adjuvant setting have yielded inconsistent results. Starting bisphosphonates in patients at any stage of their nonosseous disease, outside of clinical trials, despite a high risk for future bone metastasis, is currently not recommended. Oral bisphosphonates are one of several options which can be used for preservation of bone density in premenopausal patients with treatment-induced menopause. The panel suggests that, once initiated, IV bisphosphonates be continued until evidence of substantial decline in a patient's general performance status. The panel stresses that clinical judgment must guide what is a substantial decline. There is no evidence addressing the consequences of stopping bisphosphonates after one or more adverse skeletal events. Symptoms in the spine, pelvis, or femur require careful evaluation for spinal cord compression and pathologic fracture before bisphosphonate use and if symptoms recur, persist, or worsen during therapy. The panel recommends that current standards of care for cancer pain, analgesics and local radiation therapy, not be displaced by bisphosphonates. IV pamidronate is recommended in women with pain caused by osteolytic metastasis to relieve pain when used concurrently with systemic chemotherapy and/or hormonal therapy, since it was associated with a modest pain control benefit in controlled trials. Bisphosphonates provide a meaningful supportive but not life-prolonging benefit to many patients with bone metastases from cancer. Further research is warranted to identify clinical predictors of when to start and stop therapy, to integrate their use with other treatments for bone metastases, to identify their role in the adjuvant setting in preventing bone metastases, and to better determine their cost-benefit consequences.
    Journal of Clinical Oncology 04/2000; 18(6):1378-91. · 18.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bisphosphonate drugs are a group of pyrophosphate analogues which bind avidly to hydroxyapatite bone mineral surfaces and their major action is to inhibit osteoclast activity and thus bone resorption. In oncology, their role in metastatic bone disease is well established, but there is increasing interest in their potential role in preventing and treating cancer-induced bone loss and their possible anti-tumour effects. Metastatic bone disease is associated with a variety of skeletal complications, including pathologic fractures, bone pain, impaired mobility, spinal cord compression and hypercalcaemia. Intravenous bisphosphonates, particularly zoledronic acid, in conjunction with rehydration, are now established as the treatment of choice for hypercalcaemia. For treatment of bone pain, it has also been shown that bisphosphonates can be an effective supplementary approach to radiotherapy. In breast cancer and myeloma, bisphosphonates have now become part of standard therapy to treat and prevent skeletal-related events (SRE) and, until recently, treatment was largely with intravenous pamidronate or oral clodronate. However, large, randomised, multicentre trials using intravenous administration of the highly potent bisphosphonate zoledronic acid every 3-4 weeks have recently demonstrated a reduction of 20% in the risk of developing an SRE compared with pamidronate for patients with breast cancer. Moreover, these trials have demonstrated, for the first time, that a bisphosphonate significantly reduces the occurrence of skeletal events in hormone-refractory prostate cancer and in non-small cell lung cancer and a range of other solid tumours. Investigations into the potential of the relatively low potency bisphosphonate, clodronate, for the prevention of bone metastases in breast cancer have produced conflicting data. Further large, randomised studies with clodronate and zoledronic acid are planned and until the results are available it is not possible to identify a definite adjuvant role for bisphosphonates. Evidence is accumulating in vitro that bisphosphonates are also able to directly affect tumour cells, in addition to their effects on osteoclasts, with zoledronic acid being particularly potent. Over recent decades there has been a significant improvement in cure rates and survival times in certain cancers and the use of chemotherapy and hormone therapy has expanded greatly, leading to increasing numbers of long-term survivors who have received these treatments. Management of treatment-induced bone loss is therefore assuming a greater importance and bisphosphonates represent an attractive treatment option in such patients. Several placebo-controlled trials using oral clodronate, oral risedronate, intravenous pamidronate and intravenous zoledronic acid have all now demonstrated benefits in reducing the loss in bone mineral density.
    Endocrine Related Cancer 07/2004; 11(2):207-24. DOI:10.1677/erc.0.0110207 · 4.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The most common human cancers --lung, breast and prostate -- have a great avidity for bone, leading to painful and untreatable consequences. What makes some cancers, but not others, metastasize to bone, and how do they alter its physiology? Some of the molecular mechanisms that are responsible have recently been identified, and provide new molecular targets for drug development.
    Nature reviews. Cancer 09/2002; 2(8):584-93. DOI:10.1038/nrc867 · 37.40 Impact Factor
Show more

Preview (4 Sources)

50 Reads
Available from

We use cookies to give you the best possible experience on ResearchGate. Read our cookies policy to learn more.