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Bisphosphonate bei malignen Knochentumoren

Bisphosphonates for malignant bone tumors

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Zusammenfassung

Bisphosphonate (BP) können tumorbedingte Komplikationen des Skeletts verhindern, reduzieren oder verzögern. Seit der Verwendung von BP hat sich das Auftreten dieser Ereignisse deutlich erniedrigt. Heute gibt es ein weites Spektrum von BP mit unterschiedlicher Potenz und Effizienz, Dosierungen und Administration, aber auch unterschiedlichen Indikationen. Bei Patienten im Frühstadium von Tumorerkrankungen, bei denen das Risiko der Entstehung einer tumorinduzierten Osteoporose besteht, sollte eine präventive BP-Therapie überlegt werden. BP werden i. Allg. gut toleriert. Allerdings zeigen sich auch Nebenwirkungen, wie das „influenza-like“ Syndrom, Arthralgien und, wenn sie oral verordnet werden, auch gastrointestinale Symptome. Manchmal muss die Dosierung der BP der Nierenfunktion und der Ausgangskreatininclearance angepasst werden. Diese Arbeit soll einen Überblick über den gegenwärtigen evidenzbasierten Gebrauch von BP bei soliden Tumoren und daraus abgeleitete mögliche klinische Empfehlungen geben.

Abstract

Bisphosphonates (BPs) are able to prevent, reduce, or delay skeletal complications caused by tumors. Since the introduction of BPs, there has been a marked reduction of skeletal events. Today we can choose from a variety of BPs with different potency, efficacy, dosing, and administration regimens, as well as BPs for different indications. For patients with tumors who have a risk of developing osteoporosis induced by the tumor or antitumor treatment, we should think of prevention. In general, BPs are well tolerated. But there are also side effects: flulike syndrome, arthralgias, or, when administered orally, gastrointestinal symptoms. In a number of cases, the dosing regime must be adjusted according to renal function and baseline creatinine clearance. This paper reviews the current evidence-based use of BPs in solid tumors and the recommendations for treatment.

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Literatur

  1. Aapro M, Abrahamsson PA, Body JJ et al (2008) Guidance on the use of bisphosphonates in solid tumours: Recommendations of an international expert panel. Ann Oncol 19: 420–432

    Article  PubMed  CAS  Google Scholar 

  2. Bauss F, Body JJ (2005) Ibandronate in metastatic bone disease: A review of preclinical data. Anticancer Drugs 16: 107–118

    Article  PubMed  CAS  Google Scholar 

  3. Berenson JR, Lichtenstein A, Porter L et al (1998) Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. J Clin Oncol 16: 593–602

    PubMed  CAS  Google Scholar 

  4. Boissier S, Magnetto S, Frappart L et al (1997) Bisphosphonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. Cancer Res 57: 3890–3894

    PubMed  CAS  Google Scholar 

  5. Boissier S, Ferreras M, Peyruchaud O et al (2000) Bisphosphonates inhibit breast and prostate carcinoma cell invasion, an early event in the formation of bone metastases. Cancer Res 60: 2949–2954

    PubMed  CAS  Google Scholar 

  6. Chirgwin JM, Guise TA (2000) Molecular mechanisms of tumor-bone interactions in osteolytic metastases. Crit Rev Eukaryot Gene Expr 10: 159–178

    PubMed  CAS  Google Scholar 

  7. Civitelli R, Napoli N, Armamento-Villareal R (2007) Use of intravenous bisphosphonates in osteoporosis. Curr Osteoporos Rep 5: 8–13

    Article  PubMed  Google Scholar 

  8. Corey E, Brown LG, Quinn JE et al (2003) Zoledronic acid exhibits inhibitory effects on osteoblastic and osteolytic metastases of prostate cancer. Clin Cancer Res 9: 295–306

    PubMed  CAS  Google Scholar 

  9. Croucher PI, De Hendrik R, Perry MJ et al (2003) Zoledronic acid treatment of 5T2MM-bearing mice inhibits the development of myeloma bone disease: Evidence for decreased osteolysis, tumor burden and angiogenesis and increased survival. J Bone Miner Res 18: 482–492

    Article  PubMed  CAS  Google Scholar 

  10. Daubiné F, Le Gall C, Gasser J et al (2007) Antitumor effects of clinical dosing regimens of bisphosphonates in experimental breast cancer bone metastasis. J Natl Cancer Inst 99: 322–330

    Article  PubMed  CAS  Google Scholar 

  11. Denoyelle C, Hong L, Vannier JP et al (2003) New insights into the actions of bisphosphonate zoledronic acid in breast cancer cells by dual RhoA-dependent and-independent effects. Br J Cancer 88: 1631–1640

    Article  PubMed  CAS  Google Scholar 

  12. Diel IJ, Solomayer EF, Costa SD et al (1998) Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engl J Med 339: 357–363

    Article  PubMed  CAS  Google Scholar 

  13. Fromigue O, Kheddoumi N, Body JJ (2003) Bisphosphonates antagonise bone growth factors’ effects on human breast cancer cells survival. Br J Cancer 89: 178–184

    Article  PubMed  CAS  Google Scholar 

  14. Fleisch H (2002) Development of bisphosphonates. Breast Cancer Res 4: 30–34

    Article  PubMed  CAS  Google Scholar 

  15. Goffinet M, Thoulouzan M, Pradines A et al (2006) Zoledronic acid treatment impairs protein geranyl-geranylation for biological effects in prostatic cells. BMC Cancer 6: 60

    Article  PubMed  CAS  Google Scholar 

  16. Green JR (2002) Bisphosphonates in cancer therapy. Curr Opin Oncol 14: 609–615

    Article  PubMed  CAS  Google Scholar 

  17. Green JR (2004) Bisphosphonates: preclinical review. Oncologist 9(Suppl 4): 3–13

    Article  PubMed  CAS  Google Scholar 

  18. Heymann D, Ory B, Gouin F et al (2004) Bisphosphonates: New therapeutic agents for the treatment of bone tumors. Trends Mol Med 10: 337–343

    Article  PubMed  CAS  Google Scholar 

  19. Holzer G, Krepler P, Koschat MA et al (2003) Bone mineral density in long-term survivors of highly malignant osteosarcoma. J Bone Joint Surg Br 85: 231–237

    Article  PubMed  CAS  Google Scholar 

  20. Hughes DE, Wright KR, Uy HL et al (1995) Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 10: 1478–1487

    Article  PubMed  CAS  Google Scholar 

  21. Jagdev SP, Coleman RE, Shipman CM et al (2001) The bisphosphonate, zoledronic acid, induces apoptosis of breast cancer cells: Evidence for synergy with paclitaxel. Br J Cancer 84: 1126–1134

    Article  PubMed  CAS  Google Scholar 

  22. Lee MV, Fong EM, Singer FR, Guenette RS (2001) Bisphosphonate treatment inhibits the growth of prostate cancer cells. Cancer Res 61: 2602–2608

    PubMed  CAS  Google Scholar 

  23. Lipton A, Theriault RL, Hortobagyi GN et al (2000) Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: Long term follow-up of two randomized placebo-controlled trials. Cancer 88: 1082–1090

    Article  PubMed  CAS  Google Scholar 

  24. Luckman SP, Hughes DE, Coxon FP et al (1998) Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res 13: 581–589

    Article  PubMed  CAS  Google Scholar 

  25. Neville-Webbe HL, Evans CA, Coleman RE, Holen I (2006) Mechanisms of the synergistic interaction between the bisphosphonate zoledronic acid and the chemotherapy agent paclitaxel in breast cancer cells in vitro. Tumour Biol 27: 92–103

    Article  PubMed  CAS  Google Scholar 

  26. Rogers MJ, Gordon S, Benford HL et al (2000) Cellular and molecular mechanisms of action of bisphosphonates. Cancer 88: 2961–2978

    Article  PubMed  CAS  Google Scholar 

  27. Ross JR, Saunders Y, Edmonds PM et al (2004) A systematic review of the role of bisphosphonates in metastatic disease. Health Technol Assess 8:1–176

    PubMed  CAS  Google Scholar 

  28. Senaratne SG, Pirianov G, Mansi JL et al (2000) Bisphosphonates induce apoptosis in human breast cancer cell lines. Br J Cancer 82: 1459–1468

    PubMed  CAS  Google Scholar 

  29. Sietsema WK, Ebetino FH, Salvagno AM, Bevan JA (1989) Antiresorptive dose-response relationships across three generations of bisphosphonates. Drugs Exp Clin Res 15: 389–396

    PubMed  CAS  Google Scholar 

  30. Van den Wyngaert T, Huizing MT, Vermorken JB (2006) Bisphosphonates and osteonecrosis of the jaw: Cause and effect or a post hoc fallacy?. Ann Oncol 17: 1197–1204

    Article  Google Scholar 

  31. Viereck V, Emons G, Lauck V et al (2002) Bisphosphonates pamidronate and zoledronic acid stimulate osteoprotegerin production by primary human osteoblasts. Biochem Biophys Res Commun 291:680–686

    Article  PubMed  CAS  Google Scholar 

  32. Weitzman R, Sauter N, Eriksen EF (2007) Critical review: Updated recommendations for the prevention, diagnosis and treatment of osteonecrosis of the jaw in cancer patients (May 2006). Crit Rev Oncol Hematol 62: 148–152

    Article  PubMed  Google Scholar 

  33. Wood J, Bonjean K, Ruetz S et al (2002) Novel anti-angiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 302: 1055–1061

    Article  PubMed  CAS  Google Scholar 

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Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin: MSD, Sanofi-Aventis, Eli Lilly, Nycomed, Servier, Novartis, Avigen. Trotz des möglichen Interessenkonflikts ist der Beitrag unabhängig und produktneutral.

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  1. Universitätsklinik für Orthopädie, Medizinische Universität, Währinger Gürtel 18–20, A-1090, Wien, Österreich

    G. Holzer

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Correspondence to G. Holzer.

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Holzer, G. Bisphosphonate bei malignen Knochentumoren. Orthopäde 38, 316–323 (2009). https://doi.org/10.1007/s00132-008-1375-5

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