Advertisement

Therapie des ossär metastasierten Mammakarzinoms mit Bisphosphonaten

  • I. J. Diel

Zusammenfassung

Knochenmetastasen im Verlauf einer Brustkrebserkrankung sind sehr häufig. Legt man die Ergebnisse umfassender Autopsiestudien zugrunde, dann sind etwa 70% aller Frauen, die am metastasierten Mammakarzinom versterben, von skelettalen Absiedlungen betroffen [1]. Entsprechend der Drei-Drittel-Regel kann man sagen, dass ein Drittel der Frauen als erstes eine ossäre Metastasierung erfährt, ein Drittel im weiteren Verlauf der Erkrankung (nach viszeraler Metastasierung), ein weiteres Drittel verstirbt ohne skelettale Absiedlungen. Bei einer geschätzten Mortalität von 30% erleidet jede 4. neuerkrankte Frau eine spätere ossäre Metastasierung. In der Bundesrepublik Deutschland (geschätzte Inzidenz: 47–50000 Fälle p.a.) wären das etwa 9000 Frauen. Die durchschnittliche Überlebenszeit nach Eintritt einer Skelettmetastasierung liegt (bei sehr großer Variationsbreite) bei 2–3 Jahren. Das heißt, dass in Deutschland jährlich etwa 22000 Patientinnen mit ossär metastasiertem Mammakarzinom Kandidatinnen für eine Bisphosphonattherapie sind [2, 3].

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. 1.
    Galasko CSB (1986) Skeletal metastases. Butterworth, LondonGoogle Scholar
  2. 2.
    Parker SL, Tong T, Bolden S, Wingo PW (1997) Cancer statistics, 1997. CA-A Cancer Journal for Clinicians. 47:5–27PubMedCrossRefGoogle Scholar
  3. 3.
    Statistisches Bundesamt (Hrsg) (1995) Statistisches Jahrbuch der Bundesrepublik Deutschland 1995 (Gesundheitswesen) Metzler und Poeschel, StuttgartGoogle Scholar
  4. 4.
    Weiss L, Gilbert AH (1981) Bone metastasis. Hall, BostonGoogle Scholar
  5. 5.
    Batson OV (1940) The function of the vertebral veins and their role in the spread of metastases. Ann Surg 112:138–149PubMedCrossRefGoogle Scholar
  6. 6.
    Coman DR, de Long RP (1951) The role of the vertebral venous system in the metastasis of cancer to the spinal column: experiments with tumor cell suspensions in rats and rabbits. Cancer 4:610–618PubMedCrossRefGoogle Scholar
  7. 7.
    Orr FW, Varani J, Gondek MD, Ward PA, Mundy GR (1979) Chemotactic response of tumor cells to products of resorbing bone. Science 203:176–179PubMedCrossRefGoogle Scholar
  8. 8.
    Mundy GR, Varani J, Orr W, Gondek MD, Ward PA (1978) Resorbing bone is chemotactic for monocytes. Nature 275:132–136PubMedCrossRefGoogle Scholar
  9. 9.
    Diel IJ, Kaufmann M, Costa SD, Holle R, von Minckwitz G, Solomayer EF, Kaul S, Bastert G (1996) Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison to nodal status. J Natl Cancer Inst 88:1652–1664PubMedCrossRefGoogle Scholar
  10. 10.
    Mundy GR (1991) Mechanism of osteolytic bone destruction. Bone 12:1–6CrossRefGoogle Scholar
  11. 11.
    Mundy GR (1995) Bone remodeling and its disorders. Dunitz, LondonGoogle Scholar
  12. 12.
    Galasko CSB (1976) Mechanism of bone destruction in the development of skeletal metastases. Nature 263:507–508PubMedCrossRefGoogle Scholar
  13. 13.
    Fleisch H, Rüssel RGG, Francis MD (1969) Diphosphonates inhibit hydroxyapatite dissolution in vitro and bone resorption in tissue culture and in vivo. Science 165:1262–1264PubMedCrossRefGoogle Scholar
  14. 14.
    Fleisch H (1997) Bisphosphonates in bone disease. From the laboratory to the patient. 3rd ed. New York London, ParthenonGoogle Scholar
  15. 15.
    Rodan GA, Fleisch H (1996) Bisphosphonates: mechanisms of action. J Clin Invest 97:2692–2696PubMedCrossRefGoogle Scholar
  16. 16.
    Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Roodman GD, Mundy GR, Boyce BF (1995) Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 10:1478–1487PubMedCrossRefGoogle Scholar
  17. 17.
    Frith JC, Mönkkönen J, Blackburn GM, Russell RG, Rogers MJ (1997) Clodronate and liposome-encapsulated clodronate are metabolized to a toxic ATP analog, adenosine 5′-(beta, gamma-dichlormethylene) triphosphate, by mammalian cells in vitro. J Bone Miner Res 12:1358–1367PubMedCrossRefGoogle Scholar
  18. 18.
    Luckman SP, Hughes DE, Coxon FP, Russell RGG, Rogers MJ (1998) Nitrogen-containing bisphosphonates inhibit the mevalonat pathway and prevent posttranslational prenylation of GTP-binding proteins. J Bone Miner Res 13:581–589PubMedCrossRefGoogle Scholar
  19. 19.
    Rogers MJ, Chilton KM, Coxon FP, Lawry J, Smith MO, Suri S, Russell RGG (1996) Bisphosphonates induce apoptosis in mouse macrophage-like cells in vitro by a nitric oxide-independent mechanism. J Bone Miner Res 11:1482–1191PubMedCrossRefGoogle Scholar
  20. 20.
    Van der Pluijm G, Vloedgraven H, van Beek E, van der Wee-Pals L, Löwik C, Papapoulos S (1996) Bisphosphonates inhibit the adhesion of breast cancer cells to bone matrices in vitro. J Clin Invest 98:698–705PubMedCrossRefGoogle Scholar
  21. 21.
    Boissier S, Magnetto S, Frappart L, Cuzin B, Ebetino FH, Delmas PD, Clezardin P (1997) Bisphosphonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrix. Cancer Res 57:3890–3894PubMedGoogle Scholar
  22. 22.
    Kanis JA (1995) Bone and cancer: pathophysiology and treatment of metastases Bone 17:101S–105SPubMedCrossRefGoogle Scholar
  23. 23.
    Averbuch SD (1993) New Bisphosphonates in the treatment of bone metastases. Cancer 72:3443–3452PubMedCrossRefGoogle Scholar
  24. 24.
    Body J J, Coleman RE, Piccart M (1996) Use of bisphosphonates in cancer patients. Cancer Treat Rev 22:265–287PubMedCrossRefGoogle Scholar
  25. 25.
    Lipton A (1997) Bisphosphonates and breast cancer. Cancer 80/8 (Suppl):1668–1673CrossRefGoogle Scholar
  26. 26.
    Payne R (1997) Mechanisms and management of bone pain. Cancer 80 (Suppl): 1608–1613PubMedCrossRefGoogle Scholar
  27. 27.
    Solomayer E-F, Diel IJ, Gollan Ch, Bastert G (2000) Metastatic breast cancer: clinical course, prognosis and efficacy of therapy related to the first site of recurrence. Breast Cancer Res Treat (in press)Google Scholar
  28. 28.
    Coleman RE, Smith P, Rubens RD (1998) Clinical course and prognostic factors following bone recurrence from breast cancer. Br J Cancer 77:336–340PubMedCrossRefGoogle Scholar
  29. 29.
    Coleman RE, Rubens RD (1985) Bone metastases and breast cancer. Cancer Treat Rev 12:251–270PubMedCrossRefGoogle Scholar
  30. 30.
    Coleman RE, Rubens RD (1987) The clinical course of bone metastases from breast cancer. Br J Cancer 55:61–66PubMedCrossRefGoogle Scholar
  31. 31.
    Theriault RL, Hortobagyi GN (1992) Bone metastasis in breast cancer. Anticancer Drugs 3:455–462PubMedCrossRefGoogle Scholar
  32. 32.
    Rubens RD, Foglman I (eds) (1992) Bone Metastases. Diagnosis and treatment. Springer, London Berlin Heidelberg New YorkGoogle Scholar
  33. 33.
    Raue F (ed) (1994) Hypercalcemia of malignancy. Springer, Berlin Heidelberg New YorkGoogle Scholar
  34. 34.
    Bruning PF, Pit MJ, de Long-Bakker M, van den Ende A, Hart A, van Enk A (1990) Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer. Br J cancer 61:308–310PubMedCrossRefGoogle Scholar
  35. 35.
    Koller A, Fill H, Kurz R, Riccabona G, Haas H (1976) Osteopathy due to methotrexate. Österr Zeitschr Onkol 3:63–69Google Scholar
  36. 36.
    Gradishar WJ, Schilsky RL (1988) Effects of cancer treatment on the reproductive system. CRC Crit Rev Oncol/Haematol 82153–82171Google Scholar
  37. 37.
    Pfeilschifter J, Diel IJ (2000) Osteoporosis due to cancer treatment. J Clin Oncol (in press)Google Scholar
  38. 38.
    Bloomfield DJ (1998) Should bisphosphonates be part of the standard therapy of patients with multiple myeloma or bone metastases from other cancers? An evidence-based review. J Clin Oncol 16:1218–1225PubMedGoogle Scholar
  39. 39.
    Pecherstorfer M, Herrmann Z, Body J J et al (1996) Randomized phase II trial comparing different doses of the bisphosphonate ibandronate in the treatment of hypercalcemia of malignancy. J Clin Oncol 14:268–276PubMedGoogle Scholar
  40. 40.
    Pecherstorfer M, Ludwig H, Schlosser K et al (1996) Administration of the bisphosphonate ibandronate (BM 21.0955) by intravenous bolus injection. J Bone Miner Res 11:587–593PubMedCrossRefGoogle Scholar
  41. 41.
    Purohit OP, Radstone CR, Anthony C et al (1995) A randomised double-blind comparison of intravenous pamidronate and clodronate in the hypercalcaemia of malignancy. Br J Cancer 72:1289–1293PubMedCrossRefGoogle Scholar
  42. 42.
    Ralston SH (1992) Medical management of hypercalcaemia. Br J Clin Pharmacol 34:11–20PubMedCrossRefGoogle Scholar
  43. 43.
    Ralston SH, Thiebaud D, Herrmann Z et al (1997) Dose-response study of ibandronate in treatment of cancer-associated hypercalcaemia. Br J Cancer 75:295–300PubMedCrossRefGoogle Scholar
  44. 44.
    Body JJ (1992) Bone metastases and tumor-induced hypercalcemia. Current Opin Oncol 4:624–631CrossRefGoogle Scholar
  45. 45.
    Body JJ, Dumon JC (1994) Treatment of tumor-induced hypercalcaemia with the bisphosphonate pamidronate: Dose-response relationship and influence of the tumour type. Ann Oncol 5:359–363PubMedGoogle Scholar
  46. 46.
    Siris ES, Hyman GA, Canfield RE (1983) Effects of dichloromethylene diphosphonate in women with breast carcinoma metastatic to the skeleton. Am J Med 74:401–406PubMedCrossRefGoogle Scholar
  47. 47.
    Elomaa I, Blomquist C, Grohn P, Porkka L, Kairento AL, Selander K, Lamberg-Allardt C, Holmström T (1983) Long-term controlled trial of bisphosphonate in patients with osteolytic bone metastases. Lancet 1:146–149PubMedCrossRefGoogle Scholar
  48. 48.
    Paterson AHG, Powles TJ, Kanis JA, McCloskey E, Hansen J, Ashley S (1993) Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer. J Clin Oncol 11:59–65PubMedGoogle Scholar
  49. 49.
    Van Holten-Verzantvoort ATM, Kroon HM, Bijvoet OLM, Cleton FJ, Beex LVAM, Blijham G, Hermans J, Neijt JP, Papapoulos SE, Sleeboom HP, Vermey P, Zwinderman AH (1993) Palliative pamidronat treatment in patients with bone metastases from breast cancer. J Clin Oncol 11:491–498PubMedGoogle Scholar
  50. 50.
    Hortobagyi GN, Theriault RL, Porter L et al (1996) Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and bone metastases. N Engl J Med 335:1785–1791PubMedCrossRefGoogle Scholar
  51. 51.
    Hortobagyi GN, Theriault RL, Lipton A, Blayney D, Lipton A, Gluck S, Wheeler H, Allan S, Simeone J, Seaman J, Knight R, Hefferman M, Reitsma D et al (1998) Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. J Clin Oncol 16:2038–2044PubMedGoogle Scholar
  52. 52.
    Body JJ, Lichinitser MR, Diel IJ, Schlosser K, Pfarr E, Cavalli F, Dornoff V, Gorbunova VA, McCloskey E, Weiss J, Kanis JA (1999) Double-blind placebo controlled trial of intravenous ibandronate in breast cancer metastatic to bone. Proc Am Soc Clin Oncol 18:Abstr 2222Google Scholar
  53. 53.
    Diel IJ, Lichinitser MR, Body JJ, Schlosser K, Moecks J, Cavalli F, Dornoff W, Gorbunova VA, McCloskey E, Weiss J, Kanis JA (1999) Improvement of bone pain, quality of life and survival time of breast cancer patients with metastatic bone disease treated with intravenous ibandronate. Eur J Cancer 35:Supp 4, Abstr 269Google Scholar
  54. 54.
    Saarto T, Blomqvist C, Välimäki M, Mäkelä P, Sarna S, Elooma I (1997) Clodronat improves bone mineral density in postmenopausal breast cancer patients treated with adjuvant antioestogens. Br J Cancer 75:602–605PubMedCrossRefGoogle Scholar
  55. 55.
    Saarto T, Blomqvist C, Välimäki M, Mäkelä P, Sarna S, Elooma I (1997) Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes a rapid bone loss that is reduced by clodronate: a randomized study in premenopausal breast cancer patients. J Clin Oncol 15:1341–1347PubMedGoogle Scholar
  56. 56.
    Delmas PD, Balena R, Confravaux E, Hardouin C, Hardy P, Bremond A (1997) Bisphosphonate Risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer: a double-blind, placebo controlled study. J Clin Oncol 15:955–962PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2001

Authors and Affiliations

  • I. J. Diel

There are no affiliations available

Personalised recommendations