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Erschienen in: Supportive Care in Cancer 6/2010

01.06.2010 | Original Article

Zoledronic acid concurrent with either high- or reduced-dose palliative radiotherapy in the management of the breast cancer patients with bone metastases: a phase IV randomized clinical study

verfasst von: Lale Atahan, Ferah Yıldız, Mustafa Cengiz, Bunyamin Kaplan, Metin Özkan, Gozde Yazici, Mete Gündoğ, Ayfer Haydaroğlu, Aylin F. Korcum, Meriç Şengöz, Maktav Dinçer, Müge Akmansu, Kayıhan Engin, Mutlu Hayran

Erschienen in: Supportive Care in Cancer | Ausgabe 6/2010

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Abstract

Introduction

In this prospective study, the efficacy and safety of radiotherapy combined with zoledronic acid was evaluated.

Materials and methods

Breast cancer patients with painful bone metastases were randomized to either high- or reduced-dose radiotherapy. All patients received zoledronic acid (4 mg) every 28 days from the beginning of radiotherapy. Analgesic and pain scores in addition to visual analog score (VAS) for treatment satisfaction and whole-body bone scintigraphy were evaluated.

Results and conclusion

No significant differences could be found in analgesic or pain scores and bone scintigraphy results between the groups. Our results suggest that reduced-dose radiotherapy produces similar response rates and response durations when used concomitantly with zoledronic acid.
Literatur
4.
Zurück zum Zitat Coleman RE, Rubens RD (1987) The clinical course of bone metastases from breast cancer. Br J Cancer 55:61–66PubMed Coleman RE, Rubens RD (1987) The clinical course of bone metastases from breast cancer. Br J Cancer 55:61–66PubMed
5.
Zurück zum Zitat Bates T (1992) A review of local radiotherapy in the treatment of bone metastases and cord compression. Int J Radiat Oncol Biol Phys 23:217–221PubMed Bates T (1992) A review of local radiotherapy in the treatment of bone metastases and cord compression. Int J Radiat Oncol Biol Phys 23:217–221PubMed
8.
Zurück zum Zitat Gnant M, Mlineritsch B, Schippinger W et al (2008) Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density substudy. Lancet Oncol 9:840–849. doi:10.1016/S1470-2045(08)70204-3 CrossRefPubMed Gnant M, Mlineritsch B, Schippinger W et al (2008) Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density substudy. Lancet Oncol 9:840–849. doi:10.​1016/​S1470-2045(08)70204-3 CrossRefPubMed
9.
Zurück zum Zitat Hillner BE, Ingle JN, Chlebowski RT, Gralow J, Yee GC, Janjan NA, Cauley JA, Blumenstein BA, Albain KS, Lipton A, Brown S, American Society of Clinical Oncology (2003) 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 21:4042–4057. doi:10.1200/JCO.2003.08.017 CrossRefPubMed Hillner BE, Ingle JN, Chlebowski RT, Gralow J, Yee GC, Janjan NA, Cauley JA, Blumenstein BA, Albain KS, Lipton A, Brown S, American Society of Clinical Oncology (2003) 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 21:4042–4057. doi:10.​1200/​JCO.​2003.​08.​017 CrossRefPubMed
10.
Zurück zum Zitat Price P, Hoskin PJ, Easton D, Austin D, Palmer SG, Easton D, Austin D, Palmer SG, Yarnold JR (1986) Prospective randomized trial of single and multifraction radiotherapy schedules in the treatment of painful bony metastases. Radiother Oncol 6:247–255. doi:10.1016/S0167-8140(86)80191-8 CrossRefPubMed Price P, Hoskin PJ, Easton D, Austin D, Palmer SG, Easton D, Austin D, Palmer SG, Yarnold JR (1986) Prospective randomized trial of single and multifraction radiotherapy schedules in the treatment of painful bony metastases. Radiother Oncol 6:247–255. doi:10.​1016/​S0167-8140(86)80191-8 CrossRefPubMed
12.
Zurück zum Zitat Madsen EL (1983) Painful bone metastases: efficacy of radiotherapy assessed by the patients: a randomized trial comparing 4 Gy × 6 versus 10 Gy × 2. Int J Radiat Oncol Biol Phys 9:1775–1779PubMed Madsen EL (1983) Painful bone metastases: efficacy of radiotherapy assessed by the patients: a randomized trial comparing 4 Gy × 6 versus 10 Gy × 2. Int J Radiat Oncol Biol Phys 9:1775–1779PubMed
13.
Zurück zum Zitat Hartsell WF, Scott CB, Bruner DW, Scarantino CW, Ivker RA, Roach M, Suh JH, Demas WF, Movsas B, Petersen IA, Konski AA, Cleeland CS, Janjan NA, DeSilvio M (2005) Randomized trial of short- versus long- course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst 11:798–804 Hartsell WF, Scott CB, Bruner DW, Scarantino CW, Ivker RA, Roach M, Suh JH, Demas WF, Movsas B, Petersen IA, Konski AA, Cleeland CS, Janjan NA, DeSilvio M (2005) Randomized trial of short- versus long- course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst 11:798–804
14.
Zurück zum Zitat Wu JS, Wong R, Johnston M, Bezjak A, Whelan T (2003) Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases. Int J Radiat Oncol Biol Phys 55:594–605. doi:10.1016/S0360-3016(02)04147-0 PubMed Wu JS, Wong R, Johnston M, Bezjak A, Whelan T (2003) Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases. Int J Radiat Oncol Biol Phys 55:594–605. doi:10.​1016/​S0360-3016(02)04147-0 PubMed
15.
Zurück zum Zitat van den Hout WB, van der Linden YM, Steenland E, Wiggenraad RG, Kievit J, de Haes H, Leer JW (2003) Single- versus multipl- fraction radiotherapy in patients with painful bone metastases: cost-Utility analysis based on a randomized trial. J Natl Cancer Inst 95:222–229PubMedCrossRef van den Hout WB, van der Linden YM, Steenland E, Wiggenraad RG, Kievit J, de Haes H, Leer JW (2003) Single- versus multipl- fraction radiotherapy in patients with painful bone metastases: cost-Utility analysis based on a randomized trial. J Natl Cancer Inst 95:222–229PubMedCrossRef
16.
Zurück zum Zitat Sze WM, Shelley MD, Held I, Wilt TJ, Mason MD (2003) Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy- A systematic rewiev of randomized trials. Clin Oncol 15:345–352. doi:10.1016/S0936-6555(03)00113-4 CrossRef Sze WM, Shelley MD, Held I, Wilt TJ, Mason MD (2003) Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy- A systematic rewiev of randomized trials. Clin Oncol 15:345–352. doi:10.​1016/​S0936-6555(03)00113-4 CrossRef
18.
Zurück zum Zitat Flanagan AM, Chambers TJ (1991) Inhibition of bone resorption by bisphosphonates: interactions between bisphosphonates, osteoclasts, and bone. Calcif Tissue Int 49:407–415. doi:10.1007/BF02555852 CrossRefPubMed Flanagan AM, Chambers TJ (1991) Inhibition of bone resorption by bisphosphonates: interactions between bisphosphonates, osteoclasts, and bone. Calcif Tissue Int 49:407–415. doi:10.​1007/​BF02555852 CrossRefPubMed
20.
Zurück zum Zitat Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD, Ebetino FH, Rogers MJ (2001) Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorptio in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther 296:235–242PubMed Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD, Ebetino FH, Rogers MJ (2001) Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorptio in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther 296:235–242PubMed
21.
Zurück zum Zitat Alakangas A, Selander K, Mulari M, Halleen J, Lehenkari P, Mönkkönen J, Salo J, Väänänen K (2002) Alendronate disturbs vesicular trafficking in osteoclasts. Calcif Tissue Int 70:40–47. doi:10.1007/s002230010047 CrossRefPubMed Alakangas A, Selander K, Mulari M, Halleen J, Lehenkari P, Mönkkönen J, Salo J, Väänänen K (2002) Alendronate disturbs vesicular trafficking in osteoclasts. Calcif Tissue Int 70:40–47. doi:10.​1007/​s002230010047 CrossRefPubMed
24.
Zurück zum Zitat Pavlakis N, Schmidt RL, Stockler M (2005) Bisphosphonates for breast cancer. Cochrane Database Syst Rev 3:CD003474 Pavlakis N, Schmidt RL, Stockler M (2005) Bisphosphonates for breast cancer. Cochrane Database Syst Rev 3:CD003474
25.
Zurück zum Zitat Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J, Apffelstaedt J, Hussein MA, Coleman RE, Reitsma DJ, Chen BL, Seaman JJ (2003) Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer 98:1735–1744. doi:10.1002/cncr.11701 CrossRefPubMed Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J, Apffelstaedt J, Hussein MA, Coleman RE, Reitsma DJ, Chen BL, Seaman JJ (2003) Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer 98:1735–1744. doi:10.​1002/​cncr.​11701 CrossRefPubMed
26.
Zurück zum Zitat Rosen LS, Gordon DH, Dugan W Jr, Major P, Eisenberg PD, Provencher L, Kaminski M, Simeone J, Seaman J, Chen BL, Coleman RE (2004) Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion. Cancer 100:36–43. doi:10.1002/cncr.11892 CrossRefPubMed Rosen LS, Gordon DH, Dugan W Jr, Major P, Eisenberg PD, Provencher L, Kaminski M, Simeone J, Seaman J, Chen BL, Coleman RE (2004) Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion. Cancer 100:36–43. doi:10.​1002/​cncr.​11892 CrossRefPubMed
27.
Zurück zum Zitat Kohno N, Aogi K, Minami H, Nakamura S, Asaga T, Iino Y, Watanabe T, Goessl C, Ohashi Y, Takashima S (2005) Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a Randomized, Placebo-Controlled Trial. J Clin Oncol 23:3314–3321. doi:10.1200/JCO.2005.05.116 CrossRefPubMed Kohno N, Aogi K, Minami H, Nakamura S, Asaga T, Iino Y, Watanabe T, Goessl C, Ohashi Y, Takashima S (2005) Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a Randomized, Placebo-Controlled Trial. J Clin Oncol 23:3314–3321. doi:10.​1200/​JCO.​2005.​05.​116 CrossRefPubMed
28.
Zurück zum Zitat Coleman RE, Rosen LS, Gordon D, Major P, Kaminski M, Apffelstaedt J, Howell A, Chen B-L, Seaman JJ (2002) Zoledronic acid (4 mg) significantly reduces the relative risk of developing a skeletal–related event compared with pamidronate (90 mg) in patients with breast cancer and bone metastasis. Breast Cancer Res Treat 76(suppl.):355 Coleman RE, Rosen LS, Gordon D, Major P, Kaminski M, Apffelstaedt J, Howell A, Chen B-L, Seaman JJ (2002) Zoledronic acid (4 mg) significantly reduces the relative risk of developing a skeletal–related event compared with pamidronate (90 mg) in patients with breast cancer and bone metastasis. Breast Cancer Res Treat 76(suppl.):355
29.
Zurück zum Zitat Senaratne SG, Pirianov G, Mansi JL, Arnett TR, Colston KW (2000) Bisphophonates induce apoptosis in human breast cancer cell lines. Br J Cancer 82:1459–1468PubMed Senaratne SG, Pirianov G, Mansi JL, Arnett TR, Colston KW (2000) Bisphophonates induce apoptosis in human breast cancer cell lines. Br J Cancer 82:1459–1468PubMed
30.
Zurück zum Zitat Morony S, Capparelli C, Sarosi I, Lacey DL, Dunstan CR, Kostenuik PJ (2001) Osteoprotegrin inhibits osteolysis and decreases skeletal tumor burden in syngeneic and nude mouse models of experimental bone metastases. Cancer Res 61:4432–4436PubMed Morony S, Capparelli C, Sarosi I, Lacey DL, Dunstan CR, Kostenuik PJ (2001) Osteoprotegrin inhibits osteolysis and decreases skeletal tumor burden in syngeneic and nude mouse models of experimental bone metastases. Cancer Res 61:4432–4436PubMed
31.
Zurück zum Zitat van der Pluijm G, Vloedgraven H, van Beek E, van der Wee-Pals L, Löwik C, Papapoulos S (1996) Biphophonates inhibit the adhesion of breast cancer cells to bone matrices in vitro. J Clin Invest 98:698–705. doi:10.1172/JCI118841 CrossRefPubMed van der Pluijm G, Vloedgraven H, van Beek E, van der Wee-Pals L, Löwik C, Papapoulos S (1996) Biphophonates inhibit the adhesion of breast cancer cells to bone matrices in vitro. J Clin Invest 98:698–705. doi:10.​1172/​JCI118841 CrossRefPubMed
32.
Zurück zum Zitat Boissier S, Magnetto S, Frappart L, Cuzin B, Ebetino FH, Delmas PD, Clezardin P (1997) Biphophonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. Cancer Res 57:3890–3894PubMed Boissier S, Magnetto S, Frappart L, Cuzin B, Ebetino FH, Delmas PD, Clezardin P (1997) Biphophonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. Cancer Res 57:3890–3894PubMed
33.
Zurück zum Zitat Vogt U, Bielawski KP, Bosse U, Schlotter CM (2004) 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 12:1109–1114PubMed Vogt U, Bielawski KP, Bosse U, Schlotter CM (2004) 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 12:1109–1114PubMed
34.
Zurück zum Zitat Jagdev SP, Coleman RE, Shipman CM, Rostami-H A, Croucher PI (2001) The bisphosphonate, zoledronic acid, induces apoptosis of breast cancer cells: evidence for synergy with paclitaxel. Br J Cancer 84:1126–1134. doi:10.1054/bjoc.2001.1727 CrossRefPubMed Jagdev SP, Coleman RE, Shipman CM, Rostami-H A, Croucher PI (2001) The bisphosphonate, zoledronic acid, induces apoptosis of breast cancer cells: evidence for synergy with paclitaxel. Br J Cancer 84:1126–1134. doi:10.​1054/​bjoc.​2001.​1727 CrossRefPubMed
35.
Zurück zum Zitat Neville-Webbe HL, Rostami-Hodjegan A, Evans CA, Coleman RE, Holen I (2005) Sequence- and schedule-dependent enhancement of zoledronic acid induced apoptosis by doxorubicin in breast and prostate cancer cells. Int J Cancer 113:364–371. doi:10.1002/ijc.20602 CrossRefPubMed Neville-Webbe HL, Rostami-Hodjegan A, Evans CA, Coleman RE, Holen I (2005) Sequence- and schedule-dependent enhancement of zoledronic acid induced apoptosis by doxorubicin in breast and prostate cancer cells. Int J Cancer 113:364–371. doi:10.​1002/​ijc.​20602 CrossRefPubMed
37.
Zurück zum Zitat Ural AU, Avcu F, Candir M, Guden M, Ozcan MA (2006) In vitro synergistic effects of zoledronic acid and radiation on breast cancer cells. Breast Cancer Res 8:R52. doi:10.1186/bcr1543 CrossRefPubMed Ural AU, Avcu F, Candir M, Guden M, Ozcan MA (2006) In vitro synergistic effects of zoledronic acid and radiation on breast cancer cells. Breast Cancer Res 8:R52. doi:10.​1186/​bcr1543 CrossRefPubMed
38.
Zurück zum Zitat Arrington SA, Damron TA, Mann KA, Allen MJ (2008) Concurrent administration of zoledronic acid and irradiation leads to improved bone density, biomechanical strength, and microarchitecture in a mouse model of tumor-induced osteolysis. J Surg Oncol 97:284–290. doi:10.1002/jso.20949 CrossRefPubMed Arrington SA, Damron TA, Mann KA, Allen MJ (2008) Concurrent administration of zoledronic acid and irradiation leads to improved bone density, biomechanical strength, and microarchitecture in a mouse model of tumor-induced osteolysis. J Surg Oncol 97:284–290. doi:10.​1002/​jso.​20949 CrossRefPubMed
Metadaten
Titel
Zoledronic acid concurrent with either high- or reduced-dose palliative radiotherapy in the management of the breast cancer patients with bone metastases: a phase IV randomized clinical study
verfasst von
Lale Atahan
Ferah Yıldız
Mustafa Cengiz
Bunyamin Kaplan
Metin Özkan
Gozde Yazici
Mete Gündoğ
Ayfer Haydaroğlu
Aylin F. Korcum
Meriç Şengöz
Maktav Dinçer
Müge Akmansu
Kayıhan Engin
Mutlu Hayran
Publikationsdatum
01.06.2010
Verlag
Springer-Verlag
Erschienen in
Supportive Care in Cancer / Ausgabe 6/2010
Print ISSN: 0941-4355
Elektronische ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-009-0663-x

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