| zurück
Home |
Mamma - Karzinom: Biphosphonat - Therapie |
| allgemeines |
Biphosphonate hemmen den
Knochenabbau durch Osteoklasten und damit die Progression von
Knochenmetastasen |
Studie / Autor |
Therapie |
Standard |
Knochen - Ereignisse: HR, hazard ratio; NTX,
N-telopeptide levels; OS, overall survival; SC, subcutaneous; SRE,
skeletal-related event; SMPR, skeletal morbidity period rate; Rate der
Skeletmorbidität, skeletal morbidity rate; RR, risk ratio. |
Paterson et al. (1) |
Clodronate 1600 mg oral |
Placebo |
terminale hyperkalzaemische Episoden gesenkt(17 vs.
7; p<0.05); Wirbelbrüche geringer (124 vs. 84 events per 100 patient years; p<
0.025); Rate der Wirbelverformungen geringer (252 vs. 168; p< 0.001); Rate der
Skeletmorbidität geringer (305 to 219 per patient years; p< 0.001);
Überlebenszeit gleich |
Kristensen et al (2) |
Clodronate 1600 mg oral |
Placebo |
Zeit bis zum ersten Skelet-Ereignis höher (p<0.015);
Zahl der Frakturen geringer (5 vs. 14; p< 0.023);Skelet - Ereignisse effects are
not durable |
Tubiana-Hulin et al (3) |
Clodronate 1600 mg oral |
Placebo |
Zeit bis zum ersten Skelet-Ereignis höher (180 vs.
244 days; p = 0.05); Schmerzintensität geringer (p=0.01); Gebrauch von
Analgetika geringer(67 vs. 84%; p=0.02) |
Conte et al. (4) |
Pamidronate (45 mg IV) |
Placebo |
Zeit bis zur Progression höher (249 vs. 168 days;
p = 0.02; t by 48%); Schmerzverminderung höher (30 vs. 44% of patients; p =
0.025) |
Hortobagyi et al. (5) |
Pamidronate (90 mg IV) |
Placebo |
patients with Rate von Skeletereignissen geringer
at 15,18, 21, and 24 months (p< 0.001); Zeit bis zum ersten Skelet-Ereignis
geringer (7 vs. 13.9 months; p< 0.001); Überleben gleich
|
Theriault et al. (6) |
Pamidronate (90 mg IV) |
Placebo |
Rate der Skeletmorbidität geringer at 12 months (3.6
vs. 2.4; p=0.028), 18 months (3.7 vs. 2.4; p= 0.023), and 24 months (3.8 vs.
2.4; p = 0.008);Skelet-Komplikationen geringer (56 vs. 67%; p = 0.049) |
Body et al (7) |
Ibandronate (6 mg IV) |
Placebo |
SMPR geringer( by 20%; 1.48 vs. 1.19 periods per
patient year; p = 0.004); Zeit bis zum ersten Skelet-Ereignis geringer (50.6 vs.
33.1 weeks; p=0.018); risk of new bone events geringer(38%) |
Body et al (8) |
Ibandronate (50 mg/day oral) |
Placebo |
mean SMPR geringer (1.18 vs. 0.95; p=0.004); risk of
Rate von Skeletereignissen geringer (HR = 0.62; 95% Cl, 0.48-0.79; p< 0.0001);
No significant difference in % of patients with Rate von Skeletereignissen or
time to Rate von Skeletereignissen |
Kohno etal (9) |
Zoledronic acid (4 mg IV) |
Placebo |
Rate von Skeletereignissen geringer (p = 0.027); in
% of patients with > 1 Rate von Skeletereignissen geringer (49.6 vs. 29.8%; p =
0.003); Zeit bis zum ersten Skelet-Ereignis geringer (364 days vs. median not
reached; p= 0.007); risk of Rate von Skeletereignissen geringer(by 41% geringer
; RR = 0.59; 95% Cl, 0.38-0.91; p= 0.019); bone pain geringer (32 vs. 45% of
patients) |
Rosen et al (10) |
Zoledronic acid (4 mg IV) |
Pamidronate (90 mg IV) |
Similar rate of Rate von Skeletereignissen and Zeit
bis zum ersten Skelet-Ereignis, risk of skeletal events geringer ( by 20%
geringer; HR = 0.80; p = 0.04); risk of skeletal events geringer in patients
with osteolytic lesions (30%) and Zeit bis zum ersten Skelet-Ereignis (174 vs.
310 days; p = 0.013) |
Body et al (11) |
Denosumab (0.1, 0.3,1.0, or 3.0 mg/kg SC) |
Pamidronate (90 mg IV) |
Sustained geringer in urinary and serum NTX in
denosumab-treated patients |
Stopeck et al (12) |
Denosumab (120 mg SC) |
Zoledronic acid (4 mg IV) |
time to first on-study Rate von Skeletereignissen
geringer (HR = 0.82; 95% Cl, 0.71-0.95; p< 0.0001 noninferiority; p = 0.01
superiority); time to first and subsequent on-study Rate von Skeletereignissen
geringer (rate ratio 0.77; 95% Cl, 0.66-0.89; p=0.001); time to first radiation
to bone geringer (HR = 0.74; 95% Cl, 0.59-0.94; p=0.01); time to first on-study
Rate von Skeletereignissen geringer (HR = 0.82; 95% Cl, 0.70-0.95; p = 0.007);
mean Rate der Skeletmorbidität geringer (0.45 vs. 0.58, respectively; p= 0.004);
patients experiencing >1 on-study Rate von Skeletereignissen geringer
(denosumab: 30.7%; zoledronic acid: 36.5%) |
Diel et al (13) |
Clodronate (1600 mg/day) |
Placebo |
Similar rates of bone metastasis (23.6 vs. 26.2%)
(Median 103-month follow-up), deaths geringer (20.4 vs. 40.7%; p= 0.049) |
Powles et al. (14) |
Clodronate (1600 mg/day) |
Placebo |
risk of bone metastasis geringer (HR = 0.69; 95% Cl,
0.48-0.99; p=0.04) (5-year follow-up), risk of death geringer (HR = 0.77; p=
0.048) |
Saarto et al (15) |
Clodronate (1600 mg/day) |
nichts |
Similar rates of bone metastasis (42 vs. 32%)
(10-year follow-up) treatment No difference in OS, DFS geringer (45 vs. 58%; p =
0.01) |
ZO-FAST (16) |
Upfront zoledronic acid (4 mg every 6 41 % |
nichts |
41 % geringeres Risiko of DFS events (HR - 0.59; p =
0.031). 1035 Rezeptor-posizive Patientinnen Stadium I - IIIa. Adjuvant Letrezol
und Zoladex. Gruppe A: upfront, gruppe B: Zoladex erst bei zu geringer
Knochendichte oder Fraktur. Tumorereignisse: upfront: 42, delayed: 62. |
ABCSG-12 (17) |
Zoledronic acid |
nichts |
DFS höher (HR = 0.68; 95% Cl, 0.51-0.91; p = 0.008)
Nonsignificant anstieg in OS (HR 0.61; 95% Cl, 0.41-1.09; p = 0.09)1803
Patientinnen, Rezeptor-positiv, Stadium I und II. Tumorereignisse: mit Zoladex
54/899, ohne Zoladex 82/904 |
AZURE (18) |
Zoledronic acid |
nichts |
Größe des restlichen invasiven Tumors geringer
(15.5 mm vs. 27.4 mm; p = 0.006) |
NSABP-B34 (19) |
Clodronat |
nichts |
|
OPTIMIZE-2 |
Efficacy and safety of continued zoledronic acid every 4 weeks versus every 12 weeks in women with bone metastases from breast cancer. |
Quellen |
1. Paterson AHG, Powles TJ, Kanis JA, et al.:
Double-blind controlled trial of oral clodronate in patients with bone
metastases from breast cancer.
J Clin Oncol 1993;11:59-65
2. Kristensen B, Ejlertsen B, Groenvold M, et al.
Oral clodronate in breast cancer patients with bone metastases: a randomized
study.
J Intern Med 1999; 246:67-74
3. Tubiana-Hulin M, Beuzeboc P, Mauriac L, et al.:
[Double-blinded controlled study comparing clodronate versus placebo in patients
with breast cancer bone metastases].
Bull Cancer 2001;88:701-7
4. Conte PF, Latreille J, Mauriac L, et al.:
The Aredia Multinational Cooperative Group. Delay in progression of bone
metastases in breast cancer patients treated with intravenous Pamidronate:
results from a multinational random- ized controlled trial.
J Clin Oncol 1996;14:2552-9
5. Hortobagyi GN, Theriault RL, Lipton A, et al.:
Protocol 19 Aredia Breast Cancer Study Group. Long-term prevention of skeletal
complications of metastatic breast cancer with Pamidronate.
J Clin Oncol 1998;16:2038-44
6. Theriault RL, Lipton A, Hortobagyi GN, et al.:
Protocol 18 Aredia Breast Cancer Study Group. Pamidronate reduces skeletal
morbidity in women with advanced breast cancer and lytic bone lesions: a
randomized, placebo- controlled trial.
J Clin Oncol 1999;17:846-54
7. Body JJ, Diel IJ, Lichinitser MR, et al.:
Intravenous ibandronate reduces the incidence of skeletal complications in
patients with breast cancer and bone metastases.
Ann Oncol 2003;14:1399-405
8. Body JJ, Diel IJ, Lichinitzer M, et al.:
Oral ibandronate reduces the risk of skeletal complications in breast cancer
patients with metastatic bone disease: results from two randomised,
placebo-controlled phase III studies.
Br J Cancer 2004;90:1133-7
9. Kohno N, Aogi K, Minami H, et al.:
Zoledronic acid significantly reduces skel- etal complications compared with
placebo in Japanese women with bone metastases from breast cancer: a randomized,
placebo-controlled trial.
J Clin Oncol 2005;23:3314-21
10. Rosen LS, Gordon DH, Dugan Jr W, et al.:
Zoledronic acid is superior to Pamidronate for the treatment of bone metastases
in breast Carcinoma patients with at least one osteolytic lesion.
Cancer 2004;100:36-43
11. Body JJ, Facon T, Coleman RE, et al.:
A study of the biological receptor activator of nuclear factor-Kß ligand
inhibitor, denosumab, in patients with multiple myeloma or bone metastases from
breast cancer.
Clin Cancer Res 2006;12:1221-8
12. Stopeck A, de Boer R, Fujiwara Y, et al.:
A comparison of denosumab ver- sus zoledronic acid for the prevention of
skeletal-related events in breast cancer patients with bone metastases.
Cancer Res 2009;69(24 Suppl): Abstract 22
13. Diel IJ, Solomayer EF, Costa SD, et al.:
Reduction in new metastases in breast cancer with adjuvant clodronate treatment.
N Engl J Med 1998;339: 357-63
13a. Diel IJ, Jaschke A, Solomayer EF, et al.:
Adjuvant oral clodronate improves the overall survival of primary breast cancer
patients with micro- metastases to the bone marrow: a long-term follow-up.
Ann Oncol 2008;19:2007-11
14. Powles T, Paterson A, McCIoskey 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
15. Saarto T, Vehmanen L, Virkkunen P, et al.:
Ten-year follow-up of a randomized controlled trial of adjuvant clodronate
treatment in node-positive breast Cancer patients.
Acta Oncol 2004;43:650-6
16. Eidtmann H, de Boer R, Bundred N, et al.:
Efficacy of zoledronic acid in postmenopausal womenwith early breast
cancerreceiving adjuvant letrezole: 36-momth results of the ZO-FAST Study.
Annal Oncol 2010 Epub aheasd of print
16a. Brufsky AM et al.::
Zoledronic acid effectively prevents aromatase inhibitor-associated bone loss in
postmenopausal women with early breast cancer receiving adjuvant letresol:
Z-FAST study 36-month follow-up results.
Clin Breast Cancer 9(2009):77-85
17. Gnant M, Mlineritsch B, Stoeger H, et al.:
Mature results from ABCSG-12: adjuvant ovarian suppression combined with
tamoxifen or anastrozole, alone or in combination with zoledronic acid, in
premenopausal women with endocrine-responsive early breast cancer.
J Clin Oncol 2010;28: Abstract 533
18. Coleman RE, Winter MC, Cameron D, et al.:
The effects of adding zoledronic acid to neoadjuvant chemotherapy on tumour
response: exploratory evi- dence for direct anti-tumour activity in breast
Cancer.
Br J Cancer 2010; 102:1099-105
19.) Paterson AHG, et al.::
NSABP protocol B-34: a clinical trial comparing adjuvant clodronat vs. placebo
in early stage breast cancer patients receiving systemic chemotherapy ang/or
tamoxifen or no therapy - final analysis.
Cancer Res 71(2011):100s
|
Teil von |
Mamma - Karzinom: Studien |
Mamma - Karzinom: StudienMamma - Karzinom |
Gynäkologische Onkologie |
 |