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Insulin growth factor and bone mets - drug CLODRONATE


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Not sure how accurate this article is ...

" ... The molecular mechanisms by which tumor cells degrade bone involve tumor cell adhesion to bone as well as the release of toxic chemicals from tumor cells that stimulate osteoclast-induced bone degradation. Bisphosphonates inhibit both cancer-cell adhesion to the bone matrix and (as noted) osteoclast activity. By preventing tumor cell adhesion, biphosphonates are useful agents for the prophylactic treatment of patients with cancer that is known to preferentially metastasize to bone.

There is evidence that growth factors such as insulin-like growth factor and transforming growth factor are released when the bone matrix is degraded. These growth factors could stimulate tumor cell proliferation throughout the body, which may be a reason that early use of clodronate has significantly improved survival.



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It seems from this research that clodronate is NOT effective and actually may make things worse

http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract

Adjuvant clodronate treatment does not reduce the frequency of skeletal metastases in node-positive breast cancer patients: 5-year results of a randomized controlled trial.

Saarto T, Blomqvist C, Virkkunen P, Elomaa I.

Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.

PURPOSE: Bisphosphonates have effectively reduced the development and progression of bone metastases in advanced breast cancer. The aim of this study was to determine whether bone metastases could be prevented by adjuvant clodronate treatment in patients with primary breast cancer. PATIENTS AND METHODS: Between 1990 and 1993, 299 women with primary node-positive breast cancer were randomized to clodronate (n = 149) or control groups (n = 150). Clodronate 1,600 mg daily was given orally for 3 years. All patients received adjuvant therapy: premenopausal six cycles of CMF chemotherapy and postmenopausal antiestrogens (randomized to tamoxifen 20 mg or toremifene 60 mg/d for 3 years). Seventeen patients were excluded from the analyses because of major protocol violations. The final population was 282 patients. Intent-to-treat analyses were also performed for all major end points. The follow-up time was 5 years for all patients. RESULTS: Bone metastases were detected equally often in the clodronate and control groups: 29 patients (21%) versus 24 patients (17%) (P: = .27). The development of nonskeletal recurrence was significantly higher in the clodronate group compared with controls: 60 patients (43%) versus 36 patients (25%) (P: = .0007). The overall survival (OS) and disease-free survival (DFS) rates were also significantly lower in the clodronate group than in the controls (OS, 70% v 83%, P: = .009; DFS, 56% v 71%, P: = .007, respectively). In multivariate analyses, clodronate remained significantly associated with DFS (P: = .009). CONCLUSION: Adjuvant clodronate treatment does not prevent the development of bone metastases in node-positive breast cancer patients. However, clodronate seems to have a negative effect on DFS by increasing the development of nonskeletal metastases.

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Prevention of bone metastases from breast cancer by adjuvant bisphosphonate therapy.

Kohno N, Kokufu I.

Department of Surgery, Hyogo Medical Center for Adults 13-70, Kitaoji-cho Akashi City, Hyogo 673-8558, Japan.

There is increasing evidence regarding the importance of osteoclast activation in the pathogenesis of bone metastases. Cancer cells produce osteoclast-activating factors which play an important role in the development of bone metastases. Bisphosphonates are drugs that inhibit bone turnover by decreasing bone resorption. In patients with bone metastases from breast cancer, the effectiveness of bisphosphonate is well established for reducing skeletal complications, such as bone pain, pathological fracture, bone surgery and hypercalcemia. Recent attention has focused on a possible preventive effect on bisphosphonates of bone metastases. Animal models have supported the prevention of bone metastasis by bishosphonate therapy, but three major adjuvant clinical trials of the oral bisphosphonate clodronate have yielded conflicting results. However, our preliminary trial of intravenous bisphosphonate with pamidronate showed effective inhibition of bone metastases. Use of bisphosphonates as adjuvant therapy is still investigational yet promising. Several more randomized trials are underway to further investigate adjuvant therapy with bisphosphonates

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