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Erschienen in: Drugs 12/2015

01.08.2015 | Current Opinion

Navigating the Challenges of Endocrine Treatments in Premenopausal Women with ER-Positive Early Breast Cancer

verfasst von: Marco Colleoni, Elisabetta Munzone

Erschienen in: Drugs | Ausgabe 12/2015

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Abstract

Endocrine therapy is a key component of adjuvant treatment for premenopausal patients with endocrine-responsive tumors. It is commonly well tolerated, although side effects are a main concern in the selection of treatment options. Tamoxifen is still considered an adequate endocrine therapy in a large group of premenopausal patients (e.g. lower-risk patient, presence of co-morbidities, patient preference). Results of the SOFT and TEXT trials addressing new adjuvant endocrine treatment options in premenopausal patients were recently presented. Overall, in the SOFT study the premenopausal population did not benefit from the addition of ovarian function suppression (OFS). Nevertheless, for women at sufficient risk of recurrence to receive adjuvant chemotherapy and who maintained premenopausal estradiol, the addition of OFS to tamoxifen reduced the risk of recurrence. The magnitude of the effect was larger in younger patients. Moreover, in the SOFT and TEXT trials, adjuvant treatment with exemestane plus OFS, as compared with tamoxifen plus OFS, significantly improved disease-free survival, breast cancer-free interval and distant disease-free survival. However, premenopausal patients include heterogeneous subsets of women and tumors where costs and benefits of adjuvant endocrine therapy should be properly weighted. Issues specific for premenopausal patients, related to desire for pregnancy, family planning, safety, quality of life and subjective side effects, should be a priority in the therapeutic algorithm. Therefore, selecting the best-tolerated agent can enhance adherence to therapies and reduce the impact on quality of life and health status for these younger patients.
Literatur
1.
Zurück zum Zitat Howlader N, Noone A, Krapcho M, et al. SEER Cancer Statistics Review 1975–2008 National Cancer Institute SEER Cancer Statistics Review 1975–2008 National Cancer Institute. Cancer. 2011;2006:1992–2008. Howlader N, Noone A, Krapcho M, et al. SEER Cancer Statistics Review 1975–2008 National Cancer Institute SEER Cancer Statistics Review 1975–2008 National Cancer Institute. Cancer. 2011;2006:1992–2008.
4.
Zurück zum Zitat Goldhirsch A, Gelber RD, Yothers G, et al. Adjuvant therapy for very young women with breast cancer: need for tailored treatments. J Natl Cancer Inst Monogr. 2001;30:44–51.CrossRefPubMed Goldhirsch A, Gelber RD, Yothers G, et al. Adjuvant therapy for very young women with breast cancer: need for tailored treatments. J Natl Cancer Inst Monogr. 2001;30:44–51.CrossRefPubMed
5.
Zurück zum Zitat Berglund G, Nystedt M, Bolund C, Sjoden PO, Rutquist LE. Effect of endocrine treatment on sexuality in premenopausal breast cancer patients: a prospective randomized study. J Clin Oncol. 2001;19:2788–96.PubMed Berglund G, Nystedt M, Bolund C, Sjoden PO, Rutquist LE. Effect of endocrine treatment on sexuality in premenopausal breast cancer patients: a prospective randomized study. J Clin Oncol. 2001;19:2788–96.PubMed
6.
Zurück zum Zitat Colleoni M, Giobbie-Hurder A. Benefits and adverse effects of endocrine therapy. Ann Oncol. 2010;21 Suppl 7(suppl_7):vii107–vii111. doi:10.1093/annonc/mdq281. Colleoni M, Giobbie-Hurder A. Benefits and adverse effects of endocrine therapy. Ann Oncol. 2010;21 Suppl 7(suppl_7):vii107–vii111. doi:10.​1093/​annonc/​mdq281.
7.
Zurück zum Zitat Bentzon N, During M, Rasmussen BB, Mouridsen H, Kroman N. Prognostic effect of estrogen receptor status across age in primary breast cancer. Int J Cancer. 2008;122:1089–1094. PM:17960621. Bentzon N, During M, Rasmussen BB, Mouridsen H, Kroman N. Prognostic effect of estrogen receptor status across age in primary breast cancer. Int J Cancer. 2008;122:1089–1094. PM:17960621.
8.
9.
Zurück zum Zitat Kim EK, Noh WC, Han W, Noh DY. Prognostic significance of young age (<35 Years) by subtype based on ER, PR, and HER2 status in breast cancer: a nationwide registry-based study. World J Surg. 2011;35:1244–53. doi:10.1007/s00268-011-1071-1.CrossRefPubMed Kim EK, Noh WC, Han W, Noh DY. Prognostic significance of young age (<35 Years) by subtype based on ER, PR, and HER2 status in breast cancer: a nationwide registry-based study. World J Surg. 2011;35:1244–53. doi:10.​1007/​s00268-011-1071-1.CrossRefPubMed
13.
Zurück zum Zitat Bharat A, Aft RL, Gao F, Margenthaler JA. Patient and tumor characteristics associated with increased mortality in young women (< or = 40 years) with breast cancer. J Surg Oncol. 2009;100:248–51. doi:10.1002/jso.21268.CrossRefPubMed Bharat A, Aft RL, Gao F, Margenthaler JA. Patient and tumor characteristics associated with increased mortality in young women (< or = 40 years) with breast cancer. J Surg Oncol. 2009;100:248–51. doi:10.​1002/​jso.​21268.CrossRefPubMed
17.
Zurück zum Zitat Cancello G, Maisonneuve P, Rotmensz N, et al. Prognosis and adjuvant treatment effects in selected breast cancer subtypes of very young women (<35 years) with operable breast cancer. Ann Oncol. 2010;21:1974–81. doi:10.1093/annonc/mdq072.CrossRefPubMed Cancello G, Maisonneuve P, Rotmensz N, et al. Prognosis and adjuvant treatment effects in selected breast cancer subtypes of very young women (<35 years) with operable breast cancer. Ann Oncol. 2010;21:1974–81. doi:10.​1093/​annonc/​mdq072.CrossRefPubMed
22.
Zurück zum Zitat Ravdin RG, Lewison EF, Slack NH, et al. Results of a clinical trial concerning the worth of prophylactic oophorectomy for breast carcinoma. Surg Gynecol Obstet. 1970;131(6):1055–64.PubMed Ravdin RG, Lewison EF, Slack NH, et al. Results of a clinical trial concerning the worth of prophylactic oophorectomy for breast carcinoma. Surg Gynecol Obstet. 1970;131(6):1055–64.PubMed
23.
Zurück zum Zitat Early Breast Cancer Trialists’ Collaborative Group. (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–717. doi:10.1016/S0140-6736(05)66544-0.CrossRef Early Breast Cancer Trialists’ Collaborative Group. (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–717. doi:10.​1016/​S0140-6736(05)66544-0.CrossRef
28.
Zurück zum Zitat van Poppel H, Tombal B, de la Rosette JJ, Persson B-E, Jensen J-K, Kold Olesen T. Degarelix a novel gonadotropin-releasing hormone (GnRH) receptor blocker–results from a 1-yr, multicentre, randomised, phase 2 dosage-finding study in the treatment of prostate cancer. Eur Urol. 2008;54(4):805–13. doi:10.1016/j.eururo.2008.04.065.CrossRefPubMed van Poppel H, Tombal B, de la Rosette JJ, Persson B-E, Jensen J-K, Kold Olesen T. Degarelix a novel gonadotropin-releasing hormone (GnRH) receptor blocker–results from a 1-yr, multicentre, randomised, phase 2 dosage-finding study in the treatment of prostate cancer. Eur Urol. 2008;54(4):805–13. doi:10.​1016/​j.​eururo.​2008.​04.​065.CrossRefPubMed
30.
Zurück zum Zitat Kaufmann M, Jonat W, Kleeberg U, et al. Goserelin, a depot gonadotrophin-releasing hormone agonist in the treatment of premenopausal patients with metastatic breast cancer. German Zoladex Trial Group. J Clin Oncol. 1989;7(8):1113–9.PubMed Kaufmann M, Jonat W, Kleeberg U, et al. Goserelin, a depot gonadotrophin-releasing hormone agonist in the treatment of premenopausal patients with metastatic breast cancer. German Zoladex Trial Group. J Clin Oncol. 1989;7(8):1113–9.PubMed
31.
Zurück zum Zitat Castiglione-Gertsch M, O’Neill A, Price KN, et al. Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer: a randomized trial. J Natl Cancer Inst. 2003;95(24):1833–46.CrossRefPubMed Castiglione-Gertsch M, O’Neill A, Price KN, et al. Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer: a randomized trial. J Natl Cancer Inst. 2003;95(24):1833–46.CrossRefPubMed
32.
Zurück zum Zitat Arteaga CL, Osborne CK. Growth factors as mediators of estrogen/antiestrogen action in human breast cancer cells. In: Lippman M, Dickson R, editors. Regulatory mechanisms in breast cancer. Boston: Kluwer Academic Publishers; 1991. p. 289–304.CrossRef Arteaga CL, Osborne CK. Growth factors as mediators of estrogen/antiestrogen action in human breast cancer cells. In: Lippman M, Dickson R, editors. Regulatory mechanisms in breast cancer. Boston: Kluwer Academic Publishers; 1991. p. 289–304.CrossRef
33.
Zurück zum Zitat Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1998;351:1451–67.CrossRef Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1998;351:1451–67.CrossRef
34.
Zurück zum Zitat Davies C, Godwin J, Gray R, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378(9793):771–84. doi:10.1016/S0140-6736(11)60993-8.CrossRefPubMed Davies C, Godwin J, Gray R, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378(9793):771–84. doi:10.​1016/​S0140-6736(11)60993-8.CrossRefPubMed
35.
Zurück zum Zitat Ahn SH, Son BH, Kim SW, et al. Poor outcome of hormone receptor-positive breast cancer at very young age is due to tamoxifen resistance: nationwide survival data in Korea—a report from the Korean Breast Cancer Society. J Clin Oncol. 2007;25(17):2360–8. doi:10.1200/JCO.2006.10.3754.CrossRefPubMed Ahn SH, Son BH, Kim SW, et al. Poor outcome of hormone receptor-positive breast cancer at very young age is due to tamoxifen resistance: nationwide survival data in Korea—a report from the Korean Breast Cancer Society. J Clin Oncol. 2007;25(17):2360–8. doi:10.​1200/​JCO.​2006.​10.​3754.CrossRefPubMed
36.
Zurück zum Zitat Fisher B, Costantino J, Redmond C, et al. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med. 1989;320(8):479–84. doi:10.1056/NEJM198902233200802.CrossRefPubMed Fisher B, Costantino J, Redmond C, et al. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med. 1989;320(8):479–84. doi:10.​1056/​NEJM198902233200​802.CrossRefPubMed
38.
Zurück zum Zitat Gray RG, Rea D, Handley K et al. ATTom: long-term effects of continuing adjuvant tamoxifen to 10 Years versus stopping at 5 years in 6,953 women with early breast cancer. J Clin Oncol. 2013; (suppl; abstr 5). Gray RG, Rea D, Handley K et al. ATTom: long-term effects of continuing adjuvant tamoxifen to 10 Years versus stopping at 5 years in 6,953 women with early breast cancer. J Clin Oncol. 2013; (suppl; abstr 5).
39.
Zurück zum Zitat Burstein HJ, Temin S, Anderson H, et al. Adjuvant Endocrine Therapy for Women With Hormone Receptor-Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update. J Clin Oncol. 2014:1-16. doi:10.1200/JCO.2013.54.2258. Burstein HJ, Temin S, Anderson H, et al. Adjuvant Endocrine Therapy for Women With Hormone Receptor-Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update. J Clin Oncol. 2014:1-16. doi:10.​1200/​JCO.​2013.​54.​2258.
43.
Zurück zum Zitat Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90(18):1371–88.CrossRefPubMed Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90(18):1371–88.CrossRefPubMed
45.
Zurück zum Zitat Klijn JG, Blamey RW, Boccardo F, Tominaga T, Duchateau L, Sylvester R. Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials. J Clin Oncol. 2001;19:343–53.PubMed Klijn JG, Blamey RW, Boccardo F, Tominaga T, Duchateau L, Sylvester R. Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials. J Clin Oncol. 2001;19:343–53.PubMed
47.
Zurück zum Zitat Tevaarwerk AJ, Wang M, Zhao F, et al. Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2014;32(35):3948–58. doi:10.1200/JCO.2014.55.6993.CrossRefPubMed Tevaarwerk AJ, Wang M, Zhao F, et al. Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2014;32(35):3948–58. doi:10.​1200/​JCO.​2014.​55.​6993.CrossRefPubMed
49.
Zurück zum Zitat Davidson NE, O’Neill AM, Vukov AM, et al. Chemoendocrine therapy for premenopausal women with axillary lymph node-positive, steroid hormone receptor-positive breast cancer: results from INT 0101 (E5188). J Clin Oncol. 2005;23(25):5973–82. doi:10.1200/JCO.2005.05.551.CrossRefPubMed Davidson NE, O’Neill AM, Vukov AM, et al. Chemoendocrine therapy for premenopausal women with axillary lymph node-positive, steroid hormone receptor-positive breast cancer: results from INT 0101 (E5188). J Clin Oncol. 2005;23(25):5973–82. doi:10.​1200/​JCO.​2005.​05.​551.CrossRefPubMed
52.
Zurück zum Zitat 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(7):631–41. doi:10.1016/S1470-2045(11)70122-X.CrossRefPubMed 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(7):631–41. doi:10.​1016/​S1470-2045(11)70122-X.CrossRefPubMed
53.
Zurück zum Zitat Gnant M, Mlineritsch B, Stoeger H, et al. Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12. Ann Oncol. 2015;26(2):313–20. doi:10.1093/annonc/mdu544.CrossRefPubMed Gnant M, Mlineritsch B, Stoeger H, et al. Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12. Ann Oncol. 2015;26(2):313–20. doi:10.​1093/​annonc/​mdu544.CrossRefPubMed
56.
Zurück zum Zitat Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82. doi:10.1126/science.3798106.CrossRefPubMed Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82. doi:10.​1126/​science.​3798106.CrossRefPubMed
57.
Zurück zum Zitat Konecny G, Pauletti G, Pegram M, et al. Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. J Natl Cancer Inst. 2003;95(2):142–53.CrossRefPubMed Konecny G, Pauletti G, Pegram M, et al. Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. J Natl Cancer Inst. 2003;95(2):142–53.CrossRefPubMed
58.
Zurück zum Zitat Dowsett M, Allred C, Knox J, et al. Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the Arimidex, Tamoxifen, Alone or in Combination trial. J Clin Oncol. 2008;26(7):1059–65. doi:10.1200/JCO.2007.12.9437.CrossRefPubMed Dowsett M, Allred C, Knox J, et al. Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the Arimidex, Tamoxifen, Alone or in Combination trial. J Clin Oncol. 2008;26(7):1059–65. doi:10.​1200/​JCO.​2007.​12.​9437.CrossRefPubMed
59.
60.
Zurück zum Zitat Leary AF, Drury S, Detre S, et al. Lapatinib restores hormone sensitivity with differential effects on estrogen receptor signaling in cell models of human epidermal growth factor receptor 2-negative breast cancer with acquired endocrine resistance. Clin Cancer Res. 2010;16(5):1486–97. doi:10.1158/1078-0432.CCR-09-1764.CrossRefPubMed Leary AF, Drury S, Detre S, et al. Lapatinib restores hormone sensitivity with differential effects on estrogen receptor signaling in cell models of human epidermal growth factor receptor 2-negative breast cancer with acquired endocrine resistance. Clin Cancer Res. 2010;16(5):1486–97. doi:10.​1158/​1078-0432.​CCR-09-1764.CrossRefPubMed
61.
Zurück zum Zitat Love RR, Duc NB, Havighurst TC, et al. Her-2/neu overexpression and response to oophorectomy plus tamoxifen adjuvant therapy in estrogen receptor-positive premenopausal women with operable breast cancer. J Clin Oncol. 2003;21(3):453–7.CrossRefPubMed Love RR, Duc NB, Havighurst TC, et al. Her-2/neu overexpression and response to oophorectomy plus tamoxifen adjuvant therapy in estrogen receptor-positive premenopausal women with operable breast cancer. J Clin Oncol. 2003;21(3):453–7.CrossRefPubMed
62.
Zurück zum Zitat Hayashi N, Niikura N, Yamauchi H, Nakamura S, Ueno NT. Adding hormonal therapy to chemotherapy and trastuzumab improves prognosis in patients with hormone receptor-positive and human epidermal growth factor receptor 2-positive primary breast cancer. Breast Cancer Res Treat. 2013;137(2):523–31. doi:10.1007/s10549-012-2336-6.CrossRefPubMed Hayashi N, Niikura N, Yamauchi H, Nakamura S, Ueno NT. Adding hormonal therapy to chemotherapy and trastuzumab improves prognosis in patients with hormone receptor-positive and human epidermal growth factor receptor 2-positive primary breast cancer. Breast Cancer Res Treat. 2013;137(2):523–31. doi:10.​1007/​s10549-012-2336-6.CrossRefPubMed
63.
Zurück zum Zitat Ellis MJ, Coop A, Singh B, et al. Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial. J Clin Oncol. 2001;19(18):3808–16.PubMed Ellis MJ, Coop A, Singh B, et al. Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial. J Clin Oncol. 2001;19(18):3808–16.PubMed
67.
Zurück zum Zitat Coates AS, Winer EP, Goldhirsch A et al. Tailoring therapies-improving the management of early breast cancer: st gallen international expert consensus on the primary therapy of early breast cancer. Ann Oncol. 2015. doi:10.1093/annonc/mdv221.PubMedCentralPubMed Coates AS, Winer EP, Goldhirsch A et al. Tailoring therapies-improving the management of early breast cancer: st gallen international expert consensus on the primary therapy of early breast cancer. Ann Oncol. 2015. doi:10.​1093/​annonc/​mdv221.PubMedCentralPubMed
69.
Zurück zum Zitat Sestak I, Cuzick J, Dowsett M, et al. Prediction of Late Distant Recurrence After 5 Years of Endocrine Treatment: a combined analysis of patients from the Austrian breast and colorectal cancer study group 8 and Arimidex, tamoxifen alone or in combination randomized trials using the PAM50 risk. J Clin Oncol. 2015;33(8):916–22. doi:10.1200/JCO.2014.55.6894.CrossRefPubMed Sestak I, Cuzick J, Dowsett M, et al. Prediction of Late Distant Recurrence After 5 Years of Endocrine Treatment: a combined analysis of patients from the Austrian breast and colorectal cancer study group 8 and Arimidex, tamoxifen alone or in combination randomized trials using the PAM50 risk. J Clin Oncol. 2015;33(8):916–22. doi:10.​1200/​JCO.​2014.​55.​6894.CrossRefPubMed
72.
Zurück zum Zitat Güth U, Myrick ME, Kilic N, Eppenberger-Castori S, Schmid SM. Compliance and persistence of endocrine adjuvant breast cancer therapy. Breast Cancer Res Treat. 2011;131(2):491–9. doi:10.1007/s10549-011-1801-y.CrossRef Güth U, Myrick ME, Kilic N, Eppenberger-Castori S, Schmid SM. Compliance and persistence of endocrine adjuvant breast cancer therapy. Breast Cancer Res Treat. 2011;131(2):491–9. doi:10.​1007/​s10549-011-1801-y.CrossRef
Metadaten
Titel
Navigating the Challenges of Endocrine Treatments in Premenopausal Women with ER-Positive Early Breast Cancer
verfasst von
Marco Colleoni
Elisabetta Munzone
Publikationsdatum
01.08.2015
Verlag
Springer International Publishing
Erschienen in
Drugs / Ausgabe 12/2015
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI
https://doi.org/10.1007/s40265-015-0433-7

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