Direct and indirect anticancer activity of bisphosphonates: A brief review of published literature

Cancer Treatment Reviews

Volumn 38, Issue 5, 2012, Pages 407-415

  Gnant, Michael ^a   Clézardin, Philippe ^b  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b UNIVERSITÉ LYON 1   (France)

Author keywords

Adjuvant; Anticancer; Bisphosphonate; Bone metastases; Clodronate; Disease free survival; Survival; Zoledronic acid

Indexed keywords

ANTINEOPLASTIC AGENT; BISPHOSPHONIC ACID DERIVATIVE; CLODRONIC ACID; GERANYLTRANSFERASE; GUANINE NUCLEOTIDE BINDING PROTEIN; IBANDRONIC ACID; MEVALONIC ACID; ZOLEDRONIC ACID;

ADJUVANT CHEMOTHERAPY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BONE MARROW CELL; BONE METASTASIS; CANCER INHIBITION; CANCER INVASION; CANCER PREVENTION; CANCER SURVIVAL; CELL EXPANSION; CELL PROLIFERATION; CIRCULATING TUMOR CELL; CLINICAL TRIAL (TOPIC); DISEASE FREE SURVIVAL; DRUG SCREENING; DRUG TARGETING; ENZYME INHIBITION; GAMMA DELTA T LYMPHOCYTE; HUMAN; METASTASIS INHIBITION; MITOSIS INHIBITION; POST TREATMENT SURVIVAL; PROTEIN PRENYLATION; REVIEW; T LYMPHOCYTE ACTIVATION; TREATMENT OUTCOME; TUMOR IMMUNITY;

ANIMALS; ANTINEOPLASTIC AGENTS; BONE DENSITY CONSERVATION AGENTS; BONE MARROW; BONE NEOPLASMS; BREAST NEOPLASMS; CLINICAL TRIALS AS TOPIC; DIPHOSPHONATES; DISEASE-FREE SURVIVAL; DRUG SCREENING ASSAYS, ANTITUMOR; FEMALE; HUMANS; IMIDAZOLES; MALE; OSTEOCLASTS; PROSTATIC NEOPLASMS; TUMOR MICROENVIRONMENT;

EID: 84857280067     PISSN: 03057372     EISSN: 15321967     Source Type: Journal    
DOI: 10.1016/j.ctrv.2011.09.003     Document Type: Review

References (104)

1. Paget S. The distribution of secondary growths in cancer of the breast. Lancet 1889, 133:571-573.
2. Chambers A.F., Groom A.C., MacDonald I.C. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2002, 2:563-572.
3. Meads M.B., Hazlehurst L.A., Dalton W.S. The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance. Clin Cancer Res 2008, 14:2519-2526.
4. Shiozawa Y., Havens A.M., Pienta K.J., Taichman R.S. The bone marrow niche: habitat to hematopoietic and mesenchymal stem cells, and unwitting host to molecular parasites. Leukemia 2008, 22:941-950.
5. Russell G., Mueller G., Shipman C., Croucher P. Clinical disorders of bone resorption. Novartis Found Symp 2001, 232:251-267. discussion follows.
6. Coleman R.E. Skeletal complications of malignancy. Cancer 1997, 80:1588-1594.
7. Bellahcene A., Bachelier R., Detry C., Lidereau R., Clezardin P., Castronovo V. Transcriptome analysis reveals an osteoblast-like phenotype for human osteotropic breast cancer cells. Breast Cancer Res Treat 2007, 101:135-148.
8. Le Gall C., Bellahcene A., Bonnelye E., et al. A cathepsin K inhibitor reduces breast cancer induced osteolysis and skeletal tumor burden. Cancer Res 2007, 67:9894-9902.
9. Koeneman K.S., Yeung F., Chung L.W. Osteomimetic properties of prostate cancer cells: a hypothesis supporting the predilection of prostate cancer metastasis and growth in the bone environment. Prostate 1999, 39:246-261.
10. Bidard F.C., Vincent-Salomon A., Gomme S., et al. Disseminated tumor cells of breast cancer patients: a strong prognostic factor for distant and local relapse. Clin Cancer Res 2008, 14:3306-3311.
11. Braun S., Vogl F.D., Naume B., et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 2005, 353:793-802.
12. Cristofanilli M., Hayes D.F., Budd G.T., et al. Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 2005, 23:1420-1430.
13. Naume B., Borgen E., Kvalheim G., et al. Detection of isolated tumor cells in bone marrow in early-stage breast carcinoma patients: comparison with preoperative clinical parameters and primary tumor characteristics. Clin Cancer Res 2001, 7:4122-4419.
14. Kim M.Y., Oskarsson T., Acharyya S., et al. Tumor self-seeding by circulating cancer cells. Cell 2009, 139:1315-1326.
15. Zhang X.H., Wang Q., Gerald W., et al. Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell 2009, 16:67-78.
16. Clezardin P. Bisphosphonates' antitumor activity: an unravelled side of a multifaceted drug class. Bone 2011, 48:71-79.
17. Servier medical art. Neuilly-sur-Seine, France: Les Laboratoires Servier; 2006 [updated 14.01.08; accessed 11.03.11]. http://www.servier.com.
18. Green J., Clezardin P. The molecular basis of bisphosphonate activity: a preclinical perspective. Semin Oncol 2010, 37(Suppl. 1):S3-11.
19. Brown H.K., Ottewell P.D., Coleman R.E., Holen I. The kinetochore protein Cenp-F is a potential novel target for zoledronic acid in breast cancer cells. J Cell Mol Med 2011, 15:501-513.
20. Kunzmann V., Bauer E., Feurle J., Weissinger F., Tony H.P., Wilhelm M. Stimulation of gammadelta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma. Blood 2000, 96:384-392.
21. D'Asaro M., La Mendola C., Di Liberto D., et al. V gamma 9V delta 2 T lymphocytes efficiently recognize and kill zoledronate-sensitized, imatinib-sensitive, and imatinib-resistant chronic myelogenous leukemia cells. J Immunol 2010, 184:3260-3268.
22. Sato K., Kimura S., Segawa H., et al. Cytotoxic effects of gammadelta T cells expanded ex vivo by a third generation bisphosphonate for cancer immunotherapy. Int J Cancer 2005, 116:94-99.
23. Yuasa T., Sato K., Ashihara E., et al. Intravesical administration of gammadelta T cells successfully prevents the growth of bladder cancer in the murine model. Cancer Immunol Immunother 2008, 58:493-502.
24. Roelofs A.J., Jauhiainen M., Monkkonen H., Rogers M.J., Monkkonen J., Thompson K. Peripheral blood monocytes are responsible for gammadelta T cell activation induced by zoledronic acid through accumulation of IPP/DMAPP. Br J Haematol 2009, 144:245-250.
25. Benzaid I., Monkkonen H., Stresing V., et al. High phosphoantigen levels in bisphosphonate-treated human breast tumors promote V{gamma}9V{delta}2 T-cell chemotaxis and cytotoxicity in vivo. Cancer Res 2011, 71:4562-4572.
26. Coscia M., Quaglino E., Iezzi M., et al. Zoledronic acid repolarizes tumour-associated macrophages and inhibits mammary carcinogenesis by targeting the mevalonate pathway. J Cell Mol Med 2010, 14:2803-2815.
27. Asahi H., Mizokami A., Miwa S., Keller E.T., Koshida K., Namiki M. Bisphosphonate induces apoptosis and inhibits pro-osteoclastic gene expression in prostate cancer cells. Int J Urol 2006, 13:593-600.
28. Boissier S., Ferreras M., Peyruchaud O., et al. Bisphosphonates inhibit breast and prostate carcinoma cell invasion, an early event in the formation of bone metastases. Cancer Res 2000, 60:2949-2954.
29. Boissier S., Magnetto S., Frappart L., et al. Bisphosphonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. Cancer Res 1997, 57:3890-3894.
30. Clyburn R.D., Reid P., Evans C.A., Lefley D.V., Holen I. Increased anti-tumour effects of doxorubicin and zoledronic acid in prostate cancer cells in vitro: supporting the benefits of combination therapy. Cancer Chemother Pharmacol 2010, 65:969-978.
31. Daubine F., Le Gall C., Gasser J., Green J., Clezardin P. Antitumor effects of clinical dosing regimens of bisphosphonates in experimental breast cancer bone metastasis. J Natl Cancer Inst 2007, 99:322-330.
32. Dumon J.-C., Journe F., Kheddoumi N., Lagneaux L., Body J.-J. Cytostatic and apoptotic effects of bisphosphonates on prostate cancer cells. Eur Urol 2004, 45:521-528. discussion 8-9.
33. Hiraga T., Williams P.J., Ueda A., Tamura D., Yoneda T. Zoledronic acid inhibits visceral metastases in the 4T1/luc mouse breast cancer model. Clin Cancer Res 2004, 10:4559-4567.
34. Michailidou M., Brown H.K., Lefley D.V., et al. Microvascular endothelial cell responses in vitro and in vivo: modulation by zoledronic acid and paclitaxel?. J Vasc Res 2010, 47:481-493.
35. Miwa S., Mizokami A., Keller E.T., Taichman R., Zhang J., Namiki M. The bisphosphonate YM529 inhibits osteolytic and osteoblastic changes and CXCR-4-induced invasion in prostate cancer. Cancer Res 2005, 65:8818-8825.
36. Neville-Webbe H.L., Coleman R.E., Holen I. Combined effects of the bisphosphonate, zoledronic acid and the aromatase inhibitor letrozole on breast cancer cells in vitro: evidence of synergistic interaction. Br J Cancer 2010, 102:1010-1017.
37. Neville-Webbe H.L., Evans C.A., Coleman R.E., Holen I. Mechanisms of the synergistic interaction between the bisphosphonate zoledronic acid and the chemotherapy agent paclitaxel in breast cancer cells in vitro. Tumour Biol 2006, 27:92-103.
38. Neville-Webbe H.L., Rostami-Hodjegan A., Evans C.A., Coleman R.E., Holen I. Sequence- and schedule-dependent enhancement of zoledronic acid induced apoptosis by doxorubicin in breast and prostate cancer cells. Int J Cancer 2005, 113:364-371.
39. Ottewell P.D., Deux B., Monkkonen H., et al. Differential effect of doxorubicin and zoledronic acid on intraosseous versus extraosseous breast tumor growth in vivo. Clin Cancer Res 2008, 14:4658-4666.
40. Ottewell P.D., Lefley D.V., Cross S.S., Evans C.A., Coleman R.E., Holen I. Sustained inhibition of tumor growth and prolonged survival following sequential administration of doxorubicin and zoledronic acid in a breast cancer model. Int J Cancer 2010, 126:522-532.
41. Ottewell P.D., Monkkonen H., Jones M., Lefley D.V., Coleman R.E., Holen I. Antitumor effects of doxorubicin followed by zoledronic acid in a mouse model of breast cancer. J Natl Cancer Inst 2008, 100:1167-1178.
42. van der Pluijm G., Vloedgraven H., van Beek E., van der Wee-Pals L., Lowik C., Papapoulos S. Bisphosphonates inhibit the adhesion of breast cancer cells to bone matrices in vitro. J Clin Invest 1996, 98:698-705.
43. Vogt U., Bielawski K.P., Bosse U., Schlotter C.M. Breast tumour growth inhibition in vitro through the combination of cyclophosphamide/metotrexate/5-fluorouracil, epirubicin/cyclophosphamide, epirubicin/paclitaxel, and epirubicin/docetaxel with the bisphosphonates ibandronate and zoledronic acid. Oncol Rep 2004, 12:1109-1114.
44. Winter M.C., Holen I., Coleman R.E. Exploring the anti-tumour activity of bisphosphonates in early breast cancer. Cancer Treat Rev 2008, 34:453-475.
45. Yonou H., Ochiai A., Ashimine S., et al. The bisphosphonate YM529 inhibits osteoblastic bone tumor proliferation of prostate cancer. Prostate 2007, 67. 999-1009.
46. Fromigue O., Lagneaux L., Body J.J. Bisphosphonates induce breast cancer cell death in vitro. J Bone Miner Res 2000, 15:2211-2221.
47. Verdijk R., Franke H.R., Wolbers F., Vermes I. Differential effects of bisphosphonates on breast cancer cell lines. Cancer Lett 2007, 246:308-312.
48. Corso A., Ferretti E., Lunghi M., et al. Zoledronic acid down-regulates adhesion molecules of bone marrow stromal cells in multiple myeloma: a possible mechanism for its antitumor effect. Cancer 2005, 104:118-125.
49. Muller V., Stahmann N., Riethdorf S., et al. Circulating tumor cells in breast cancer: correlation to bone marrow micrometastases, heterogeneous response to systemic therapy and low proliferative activity. Clin Cancer Res 2005, 11:3678-3685.
50. Mundy G.R. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2002, 2:584-593.
51. Coleman R.E. Risks and benefits of bisphosphonates. Br J Cancer 2008, 98:1736-1740.
52. Aft R., Naughton M., Trinkaus K., et al. Effect of zoledronic acid on disseminated tumour cells in women with locally advanced breast cancer: an open label, randomised, phase 2 trial. Lancet Oncol 2010, 11:421-428.
53. Lin A.Y., Park J.W., Scott J., et al. Zoledronic acid as adjuvant therapy for women with early stage breast cancer and disseminated tumor cells in bone marrow. J Clin Oncol 2008, 26(Suppl.):20s. Abstract 559.
54. Rack B., Jückstock J., Genss E., et al. Effect of zoledronate on persisting isolated tumour cells in patients with early breast cancer. Anticancer Res 2010, 30:1807-1813.
55. Solomayer E., Gebauer G., Hirnle P., et al. Influence of zoledronic acid on disseminated tumor cells (DTC) in primary breast cancer patients. Cancer Res 2008, 69(Suppl.):170s-171s. Abstract 2048.
56. Greenberg S., Park J.W., Melisko M.E., et al. Effect of adjuvant zoledronic acid (ZOL) on disseminated tumor cells (DTC) in the bone marrow (BM) of women with early-stage breast cancer (ESBC): updated results. J Clin Oncol 2010, 28(Suppl.):114s. Abstract 1002.
57. Diel I.J., Jaschke A., Solomayer E.F., et al. Adjuvant oral clodronate improves the overall survival of primary breast cancer patients with micrometastases to the bone marrow: a long-term follow-up. Ann Oncol 2008, 19:2007-2011.
58. Powles T., Paterson A., McCloskey E., et al. Reduction in bone relapse and improved survival with oral clodronate for adjuvant treatment of operable breast cancer [ISRCTN83688026]. Breast Cancer Res 2006, 8:R13.
59. Coleman R.E., Winter M.C., Cameron D., et al. The effects of adding zoledronic acid to neoadjuvant chemotherapy on tumour response: exploratory evidence for direct anti-tumour activity in breast cancer. Br J Cancer 2010, 102:1099-1105.
60. Saarto T., Blomqvist C., Virkkunen P., Elomaa I. 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. J Clin Oncol 2001, 19:10-17.
61. Saarto T., Vehmanen L., Virkkunen P., Blomqvist C. Ten-year follow-up of a randomized controlled trial of adjuvant clodronate treatment in node-positive breast cancer patients. Acta Oncol 2004, 43:650-656.
62. Diel I.J., Solomayer E.F., Costa S.D., et al. Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engl J Med 1998, 339:357-363.
63. Eidtmann H., de Boer R., Bundred N., et al. Efficacy of zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36-month results of the ZO-FAST study. Ann Oncol 2010, 21:2188-2194.
64. de Boer R, Bundred N, Eidtmann H, et al. The effect of zoledronic acid on aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: the ZO-FAST study 5-year final follow-up. Poster presented at: 33rd Annual San Antonio Breast Cancer Symposium; December 8-12. San Antonio (TX); 2010. Abstract P5-11-01.
65. Gnant M., Mlineritsch B., Schippinger W., et al. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 2009, 360:679-691.
66. Gnant M., Mlineritsch B., Stoeger H., et al. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial. Lancet Oncol 2011, 12:631-641.
67. Gnant M, Mlineritsch B, Luschin-Ebengreuth G, et al. Overall survival with adjuvant zoledronic acid in premenopausal breast cancer patients with complete endocrine blockade-long-term results from ABCSG-12. Poster presented at: 2011 ASCO Annual Meeting; June 3-7. Chicago (IL); 2011. Abstract 520.
68. Coleman RE, Thorpe HC, Cameron D, et al. Adjuvant treatment with zoledronic acid in stage II/III breast cancer. The AZURE trial (BIG 01/04). Oral presentation at: 33rd Annual San Antonio Breast Cancer Symposium; December 8-12. San Antonio (TX); 2010. Abstract S4-5.
69. Dearnaley D.P., Mason M.D., Parmar M.K., Sanders K., Sydes M.R. Adjuvant therapy with oral sodium clodronate in locally advanced and metastatic prostate cancer: long-term overall survival results from the MRC PR04 and PR05 randomised controlled trials. Lancet Oncol 2009, 10:872-876.
70. Mystakidou K., Katsouda E., Parpa E., Kelekis A., Galanos A., Vlahos L. Randomized, open label, prospective study on the effect of zoledronic acid on the prevention of bone metastases in patients with recurrent solid tumors that did not present with bone metastases at baseline. Med Oncol 2005, 22:195-201.
71. Zaghloul M.S., Boutrus R., El-Hosieny H., A-Kader Y., El-Attar I., Nazmy M. A prospective, randomized, placebo-controlled trial of zoledronic acid in bony metastatic bladder cancer. Int J Clin Oncol. 2010, 15:382-389.
72. Zarogoulidis K., Boutsikou E., Zarogoulidis P., et al. The impact of zoledronic acid therapy in survival of lung cancer patients with bone metastasis. Int J Cancer 2009, 125:1705-1709.
73. Aviles A., Nambo M.J., Neri N., Castaneda C., Cleto S., Huerta-Guzman J. Antitumor effect of zoledronic acid in previously untreated patients with multiple myeloma. Med Oncol 2007, 24:227-230.
74. Morgan G.J., Davies F.E., Gregory W.M., et al. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet 2010, 376:1989-1999.
75. Gnant M. Bisphosphonates in the prevention of disease recurrence: current results and ongoing trials. Curr Cancer Drug Targets 2009, 9:824-833.
76. Reimer T, Nitz U, Potenberg J, et al. ICE study: ibandronate with or without capecitabine in elderly patients with early breast cancer. Oral presentation at: Primary Therapy of Early Breast Cancer 11th International Conference; March 11-14. St. Gallen, Switzerland; 2009. Abstract 273.
77. Möbus V, Conrad B, Schneeweiss A, et al. GAIN study: a phase III trial to compare ETC. vs. EC-TX and ibandronate vs. observation in patients with node-positive primary breast cancer. Poster presented at: Primary Therapy of Early Breast Cancer 11th International Conference; March 11-14. St. Gallen, Switzerland; 2009. Abstract 272.
78. US National Institutes of Health. Study to determine treatment effects of denosumab in patients with breast cancer receiving aromatase inhibitor therapy. 2001 [accessed 17.06.11]. http://clinicaltrials.gov/ct2/show/NCT00556374?term=nct00556374&rank=1.
79. US National Institutes of Health. Study of denosumab as adjuvant treatment for women with high risk early breast cancer receiving neoadjuvant or adjuvant therapy (D-CARE). 2011 [accessed 17.06.11]. http://clinicaltrials.gov/ct2/show/NCT01077154?term=nct01077154&rank=1.
80. Smith M, Saad F, Coleman R, et al. Denosumab to prolong bone metastasis-free survival in men with castrate-resistant prostate cancer: results of a global phase 3, randomized, double-blind trial. Oral presentation at: AUA Annual Meeting; May 14-19. Atlanta (GA); 2011.
81. Newcomb P.A., Trentham-Dietz A., Hampton J.M. Bisphosphonates for osteoporosis treatment are associated with reduced breast cancer risk. Br J Cancer 2010, 102:799-802.
82. Chlebowski R.T., Chen Z., Cauley J.A., et al. Oral bisphosphonate use and breast cancer incidence in postmenopausal women. J Clin Oncol 2010, 28:3582-3590.
83. Rennert G., Pinchev M., Rennert H.S. Use of bisphosphonates and risk of postmenopausal breast cancer. J Clin Oncol 2010, 28:3577-3581.
84. Rennert G., Pinchev M., Rennert H.S., Gruber S.B. Use of bisphosphonates and reduced risk of colorectal cancer. J Clin Oncol 2011, 29:1146-1150.
85. Coleman R., Bundred N., de Boer R., et al. Impact of zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: Z-FAST, ZO-FAST, and E-ZO-FAST. Cancer Res 2009, 69(Suppl.):733s. Abstract 4082.
86. Thurlimann B., Keshaviah A., Coates A.S., et al. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 2005, 353:2747-2757.
87. Sowers M.R., Zheng H., McConnell D., Nan B., Harlow S.D., Randolph J.F., et al. Estradiol rates of change in relation to the final menstrual period in a population-based cohort of women. J Clin Endocrinol Metab 2008, 93:3847-3852.
88. Geisler J., Haynes B., Anker G., Dowsett M., Lonning P.E. Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study. J Clin Oncol 2002, 20:751-757.
89. Geisler J., King N., Anker G., et al. In vivo inhibition of aromatization by exemestane, a novel irreversible aromatase inhibitor, in postmenopausal breast cancer patients. Clin Cancer Res 1998, 4:2089-2093.
90. Mattarollo S.R., Kenna T., Nieda M., Nicol A.J. Chemotherapy and zoledronate sensitize solid tumour cells to Vgamma9Vdelta2 T cell cytotoxicity. Cancer Immunol Immunother 2007, 56:1285-1297.
91. Cauley J.A., Lucas F.L., Kuller L.H., Vogt M.T., Browner W.S., Cummings S.R. Bone mineral density and risk of breast cancer in older women: the study of osteoporotic fractures. Study of Osteoporotic Fractures Research Group. JAMA 1996, 276:1404-1408.
92. Kuhl H. Breast cancer risk in the WHI study: the problem of obesity. Maturitas 2005, 51:83-97.
93. Saad F. New research findings on zoledronic acid: survival, pain, and anti-tumour effects. Cancer Treat Rev 2008, 34:183-192.
94. Saad F., Gleason D.M., Murray R., et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 2004, 96:879-882.
95. Rosen L.S., Gordon D., Tchekmedyian N.S., et al. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, phase III, double-blind, placebo-controlled trial. Cancer 2004, 100:2613-2621.
96. Lipton A., Zheng M., Seaman J. Zoledronic acid delays the onset of skeletal-related events and progression of skeletal disease in patients with advanced renal cell carcinoma. Cancer 2003, 98:962-969.
97. Lipton A., Cook R., Saad F., et al. Normalization of bone markers is associated with improved survival in patients with bone metastases from solid tumors and elevated bone resorption receiving zoledronic acid. Cancer 2008, 113:193-201.
98. Body J-J, Cook R, Costa L, et al. Possible survival benefits from zoledronic acid treatment in patients with bone metastases from solid tumors and poor prognostic features. Poster presented at: IX International Meeting on Cancer Induced Bone Disease; October 28-31. Arlington (VA); 2009. Abstract 71.
99. Saad F., Lipton A., Cook R., Chen Y.M., Smith M., Coleman R. Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer 2007, 110:1860-1867.
100. Berenson J.R., Lichtenstein A., Porter L., et al. Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group. J Clin Oncol 1998, 16:593-602.
101. McCloskey E.V., Dunn J.A., Kanis J.A., MacLennan I.C., Drayson M.T. Long-term follow-up of a prospective, double-blind, placebo-controlled randomized trial of clodronate in multiple myeloma. Br J Haematol 2001, 113:1035-1043.
102. Santini D., Vincenzi B., Galluzzo S., et al. Repeated intermittent low-dose therapy with zoledronic acid induces an early, sustained, and long-lasting decrease of peripheral vascular endothelial growth factor levels in cancer patients. Clin Cancer Res 2007, 13:4482-4486.
103. Zhao X., Xu X., Guo L., et al. Biomarker alterations with metronomic use of low-dose zoledronic acid for breast cancer patients with bone metastases and potential clinical significance. Breast Cancer Res Treat 2010, 124:733-743.
104. Santini D., Martini F., Fratto M.E., et al. In vivo effects of zoledronic acid on peripheral gammadelta T lymphocytes in early breast cancer patients. Cancer Immunol Immunother 2009, 58:31-38.