Skip to main content
Erschienen in: Targeted Oncology 4/2011

01.12.2011 | Review

Targeted agents: review of toxicity in the elderly metastatic colorectal cancer patients

verfasst von: Flora Kyriakou, Panteleimon Kountourakis, Demetris Papamichael

Erschienen in: Targeted Oncology | Ausgabe 4/2011

Einloggen, um Zugang zu erhalten

Abstract

Colorectal cancer remains a major cause of cancer mortality in the Western world. With a median age at presentation of 71, patients with metastatic disease are often elderly with significant co-morbidities. In addition, elderly patients are more likely to be undertreated and under-represented in clinical trials. Therefore, as the available data from clinical trials are scarce, the optimal treatment strategy for this group of patients has not been adequately defined. In the setting of metastatic colorectal cancer, the introduction of so called targeted agents has significantly improved outcomes in the context of randomized clinical trials, while at the same time increasing treatment options for such patients. This review focuses on the role of targeted therapies in elderly patients with metastatic colorectal cancer, with specific reference to toxicity and tolerability. It should be noted that studies reviewed herein will have mostly included fit elderly patients fulfilling specific inclusion criteria. The available data so far are limited but suggest that targeted agents have similar efficacy and tolerability in elderly fit patients when compared with younger ones, provided caution is exercised in specific high-risk sub-groups. Clearly, further studies aimed at this specific patient population using well-established geriatric end-points will hopefully identify those patients more likely to benefit and less likely to suffer severe side effects.
Literatur
1.
Zurück zum Zitat Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300PubMedCrossRef Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300PubMedCrossRef
2.
Zurück zum Zitat Aapro MS, Kohne CH, Cohen HJ, Extermann M (2005) Never too old? Age should not be a barrier to enrollment in cancer clinical trials. Oncologist 10:198–204PubMedCrossRef Aapro MS, Kohne CH, Cohen HJ, Extermann M (2005) Never too old? Age should not be a barrier to enrollment in cancer clinical trials. Oncologist 10:198–204PubMedCrossRef
3.
Zurück zum Zitat Berrino F, Capoccaccia R, Esteve J, Gatta G (1999) Survival of cancer patients in Europe: the EUROCARE-2 study. IARC Sci Publ 151:1–572 Berrino F, Capoccaccia R, Esteve J, Gatta G (1999) Survival of cancer patients in Europe: the EUROCARE-2 study. IARC Sci Publ 151:1–572
4.
Zurück zum Zitat Hutchins LF, Unger JM, Crowley JJ et al (1999) Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 30:2061–2067CrossRef Hutchins LF, Unger JM, Crowley JJ et al (1999) Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 30:2061–2067CrossRef
5.
Zurück zum Zitat Lewis JH, Kilgore ML, Goldman DP et al (2003) Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol 21(7):1383–1389PubMedCrossRef Lewis JH, Kilgore ML, Goldman DP et al (2003) Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol 21(7):1383–1389PubMedCrossRef
6.
Zurück zum Zitat Folprecht G, Cunningham D, Ross P et al (2004) Efficacy of 5-fluorouracil-based chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials. Ann Oncol 15(9):1330–1338PubMedCrossRef Folprecht G, Cunningham D, Ross P et al (2004) Efficacy of 5-fluorouracil-based chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials. Ann Oncol 15(9):1330–1338PubMedCrossRef
7.
Zurück zum Zitat Popescu RA, Norman A, Ross PJ et al (1999) Adjuvant or palliative chemotherapy for colorectal cancer in patients 70 years or older. J Clin Oncol 17(8):2412–2418PubMed Popescu RA, Norman A, Ross PJ et al (1999) Adjuvant or palliative chemotherapy for colorectal cancer in patients 70 years or older. J Clin Oncol 17(8):2412–2418PubMed
8.
Zurück zum Zitat Folprecht G, Seymour MT, Saltz L et al (2008) Irinotecan/fluorouracil combination in first-line therapy of older and younger patients with metastatic colorectal cancer: combined analysis of 2,691 patients in randomized controlled trials. J Clin Oncol 26(9):1443–1451PubMedCrossRef Folprecht G, Seymour MT, Saltz L et al (2008) Irinotecan/fluorouracil combination in first-line therapy of older and younger patients with metastatic colorectal cancer: combined analysis of 2,691 patients in randomized controlled trials. J Clin Oncol 26(9):1443–1451PubMedCrossRef
9.
Zurück zum Zitat Goldberg RM, Tabah-Fisch I, Bleiberg H et al (2006) Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol 24(25):4085–4091PubMedCrossRef Goldberg RM, Tabah-Fisch I, Bleiberg H et al (2006) Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol 24(25):4085–4091PubMedCrossRef
10.
Zurück zum Zitat Figer A, Perez-Staub N, Carola E et al (2007) FOLFOX in patients aged between 76 and 80 years with metastatic colorectal cancer: an exploratory cohort of the OPTIMOX1 study. Cancer 110(12):2666–2671PubMedCrossRef Figer A, Perez-Staub N, Carola E et al (2007) FOLFOX in patients aged between 76 and 80 years with metastatic colorectal cancer: an exploratory cohort of the OPTIMOX1 study. Cancer 110(12):2666–2671PubMedCrossRef
11.
Zurück zum Zitat François E, Berdah JF, Chamorey E et al (2008) Use of the folinic acid/5-fluorouracil/irinotecan (FOLFIRI) regimen in elderly patients as a first-line treatment for metastatic colorectal cancer: a Phase II study. Cancer Chemother Pharmacol 62:931–936PubMedCrossRef François E, Berdah JF, Chamorey E et al (2008) Use of the folinic acid/5-fluorouracil/irinotecan (FOLFIRI) regimen in elderly patients as a first-line treatment for metastatic colorectal cancer: a Phase II study. Cancer Chemother Pharmacol 62:931–936PubMedCrossRef
12.
Zurück zum Zitat Aparicio T, Desramé J, Lecomte T et al (2003) Oxaliplatin- or irinotecan-based chemotherapy for metastatic colorectal cancer in the elderly. Br J Cancer 89:1439–1444PubMedCrossRef Aparicio T, Desramé J, Lecomte T et al (2003) Oxaliplatin- or irinotecan-based chemotherapy for metastatic colorectal cancer in the elderly. Br J Cancer 89:1439–1444PubMedCrossRef
13.
Zurück zum Zitat Cunningham D, Humblet Y, Siena S et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337–345CrossRef Cunningham D, Humblet Y, Siena S et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337–345CrossRef
14.
Zurück zum Zitat Jonker DJ, O’Callaghan CJ, Karapetis CS et al (2009) Cetuximab for the treatment of colorectal cancer. N Engl J Med 360(14):1408–1417CrossRef Jonker DJ, O’Callaghan CJ, Karapetis CS et al (2009) Cetuximab for the treatment of colorectal cancer. N Engl J Med 360(14):1408–1417CrossRef
15.
Zurück zum Zitat Asmis TR, Powell E, Karapetis CS et al (2011) Comorbidity, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)–results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care. Ann Oncol 22(1):118–126PubMedCrossRef Asmis TR, Powell E, Karapetis CS et al (2011) Comorbidity, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)–results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care. Ann Oncol 22(1):118–126PubMedCrossRef
16.
Zurück zum Zitat Bouchahda M, Macarulla T, Spano JP et al (2008) Cetuximab efficacy and safety in a retrospective cohort of elderly patients with heavily pretreated metastatic colorectal cancer. Crit Rev Oncol Hematol 67(3):255–262PubMedCrossRef Bouchahda M, Macarulla T, Spano JP et al (2008) Cetuximab efficacy and safety in a retrospective cohort of elderly patients with heavily pretreated metastatic colorectal cancer. Crit Rev Oncol Hematol 67(3):255–262PubMedCrossRef
17.
Zurück zum Zitat Fornaro L, Baldi GG, Masi G et al (2011) Cetuximab plus irinotecan after irinotecan failure in elderly metastatic colorectal cancer patients: Clinical outcome according to KRAS and BRAF mutational status. Crit Rev Oncol Hematol 78(3):243–251PubMedCrossRef Fornaro L, Baldi GG, Masi G et al (2011) Cetuximab plus irinotecan after irinotecan failure in elderly metastatic colorectal cancer patients: Clinical outcome according to KRAS and BRAF mutational status. Crit Rev Oncol Hematol 78(3):243–251PubMedCrossRef
18.
Zurück zum Zitat Sastre J, Aranda E, Grávalos C et al (2011) First-line single-agent cetuximab in elderly patients with metastatic colorectal cancer. A phase II clinical and molecular study of the Spanish group for digestive tumor therapy (TTD). Crit Rev Oncol Hematol 77(1):78–84PubMedCrossRef Sastre J, Aranda E, Grávalos C et al (2011) First-line single-agent cetuximab in elderly patients with metastatic colorectal cancer. A phase II clinical and molecular study of the Spanish group for digestive tumor therapy (TTD). Crit Rev Oncol Hematol 77(1):78–84PubMedCrossRef
19.
Zurück zum Zitat Van Cutsem E, Köhne C-H, Hitre E et al (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. NEJM 360:1408–1417PubMedCrossRef Van Cutsem E, Köhne C-H, Hitre E et al (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. NEJM 360:1408–1417PubMedCrossRef
20.
Zurück zum Zitat Su X, Lacouture ME, Jia Y, Wu S (2009) Risk of high-grade skin rash in cancer patients treated with cetuximab—an antibody against epidermal growth factor receptor: systemic review and meta-analysis. Oncology 77(2):124–133PubMedCrossRef Su X, Lacouture ME, Jia Y, Wu S (2009) Risk of high-grade skin rash in cancer patients treated with cetuximab—an antibody against epidermal growth factor receptor: systemic review and meta-analysis. Oncology 77(2):124–133PubMedCrossRef
21.
Zurück zum Zitat Sobrero AF, Maurel J, Fehrenbacher L et al (2008) EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 26(14):2311–2319PubMedCrossRef Sobrero AF, Maurel J, Fehrenbacher L et al (2008) EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 26(14):2311–2319PubMedCrossRef
22.
Zurück zum Zitat Siena S, Glynne-Jones R, Adenis A et al (2010) Reduced incidence of infusion-related reactions in metastatic colorectal cancer during treatment with cetuximab plus irinotecan with combined corticosteroid and antihistamine premedication. Cancer 116(7):1827–1837PubMedCrossRef Siena S, Glynne-Jones R, Adenis A et al (2010) Reduced incidence of infusion-related reactions in metastatic colorectal cancer during treatment with cetuximab plus irinotecan with combined corticosteroid and antihistamine premedication. Cancer 116(7):1827–1837PubMedCrossRef
23.
Zurück zum Zitat Tejpar S, Piessevaux H, Claes K et al (2007) Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a prospective study. Lancet Oncol 8(5):387–394PubMedCrossRef Tejpar S, Piessevaux H, Claes K et al (2007) Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a prospective study. Lancet Oncol 8(5):387–394PubMedCrossRef
24.
Zurück zum Zitat Schrag D, Chung KY, Flombaum C, Saltz L (2005) Cetuximab therapy and symptomatic hypomagnesemia. J Natl Cancer Inst 97(16):1221–1224PubMedCrossRef Schrag D, Chung KY, Flombaum C, Saltz L (2005) Cetuximab therapy and symptomatic hypomagnesemia. J Natl Cancer Inst 97(16):1221–1224PubMedCrossRef
25.
Zurück zum Zitat Van Cutsem E, Peeters M, Siena S et al (2007) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25(13):1658–1664PubMedCrossRef Van Cutsem E, Peeters M, Siena S et al (2007) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25(13):1658–1664PubMedCrossRef
26.
Zurück zum Zitat Van Cutsem E, Siena S, Humblet Y et al (2008) An open-label, single-arm study assessing safety and efficacy of panitumumab in patients with metastatic colorectal cancer refractory to standard chemotherapy. Ann Oncol 19(1):92–98PubMedCrossRef Van Cutsem E, Siena S, Humblet Y et al (2008) An open-label, single-arm study assessing safety and efficacy of panitumumab in patients with metastatic colorectal cancer refractory to standard chemotherapy. Ann Oncol 19(1):92–98PubMedCrossRef
27.
Zurück zum Zitat Douillard J-Y, Siena S, Cassidy J et al (2010) Randomized, phase III trial of panitumumab with infusional Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX4) Versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 31:4697–4705CrossRef Douillard J-Y, Siena S, Cassidy J et al (2010) Randomized, phase III trial of panitumumab with infusional Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX4) Versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 31:4697–4705CrossRef
28.
Zurück zum Zitat Peeters M, Price TJ, Cervantes A et al (2010) Randomized phase III study of panitumumab with Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 31:4706–4713CrossRef Peeters M, Price TJ, Cervantes A et al (2010) Randomized phase III study of panitumumab with Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 31:4706–4713CrossRef
29.
Zurück zum Zitat Heun J, Holen K (2007) Treatment with panitumumab after a severe infusion reaction to cetuximab in a patient with metastatic colorectal cancer: a case report. Clin Colorectal Cancer 6(7):529–531PubMedCrossRef Heun J, Holen K (2007) Treatment with panitumumab after a severe infusion reaction to cetuximab in a patient with metastatic colorectal cancer: a case report. Clin Colorectal Cancer 6(7):529–531PubMedCrossRef
30.
Zurück zum Zitat Cartwright TH, Genther R (2008) Successful administration of panitumumab alone after severe infusion reaction to cetuximab in a patient with metastatic colorectal cancer. Clin Colorectal Cancer 7(3):202–203PubMedCrossRef Cartwright TH, Genther R (2008) Successful administration of panitumumab alone after severe infusion reaction to cetuximab in a patient with metastatic colorectal cancer. Clin Colorectal Cancer 7(3):202–203PubMedCrossRef
31.
Zurück zum Zitat Kabbinavar FF, Hurwitz HI, Yi J et al (2009) Addition of bevacizumab to fluorouracil-based first-line treatment of metastatic colorectal cancer: pooled analysis of cohorts of older patients from two randomized clinical trials. J Clin Oncol 27(2):199–205PubMedCrossRef Kabbinavar FF, Hurwitz HI, Yi J et al (2009) Addition of bevacizumab to fluorouracil-based first-line treatment of metastatic colorectal cancer: pooled analysis of cohorts of older patients from two randomized clinical trials. J Clin Oncol 27(2):199–205PubMedCrossRef
32.
Zurück zum Zitat Cassidy J, Saltz LB, Giantonio BJ et al (2010) Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies. J Cancer Res Clin Oncol 136(5):737–743PubMedCrossRef Cassidy J, Saltz LB, Giantonio BJ et al (2010) Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies. J Cancer Res Clin Oncol 136(5):737–743PubMedCrossRef
33.
Zurück zum Zitat Kozloff M, Yood MU, Berlin J et al (2009) Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study. Oncologist 14(9):862–870PubMedCrossRef Kozloff M, Yood MU, Berlin J et al (2009) Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study. Oncologist 14(9):862–870PubMedCrossRef
34.
Zurück zum Zitat Kozloff MF, Berlin J, Flynn PJ et al (2010) Clinical outcomes in elderly patients with metastatic colorectal cancer receiving bevacizumab and chemotherapy: results from the BRiTE observational cohort study. Oncology 78(5–6):329–339PubMedCrossRef Kozloff MF, Berlin J, Flynn PJ et al (2010) Clinical outcomes in elderly patients with metastatic colorectal cancer receiving bevacizumab and chemotherapy: results from the BRiTE observational cohort study. Oncology 78(5–6):329–339PubMedCrossRef
35.
Zurück zum Zitat Van Cutsem E, Rivera F, Berry S et al (2009) Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 20(11):1842–1847PubMedCrossRef Van Cutsem E, Rivera F, Berry S et al (2009) Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 20(11):1842–1847PubMedCrossRef
36.
Zurück zum Zitat Kubala E, Bartos J, Petruzelka LB et al (2010) Safety and effectiveness of bevacizumab (bev) in combination with chemotherapy (CT) in elderly patients (pts) with metastatic colorectal cancer (mCRC): Results from a large Czech observational registry (CSTP). Proc Am Soc Clin Oncol Gastrointest Cancer Symp 2010, Abstr 467 Kubala E, Bartos J, Petruzelka LB et al (2010) Safety and effectiveness of bevacizumab (bev) in combination with chemotherapy (CT) in elderly patients (pts) with metastatic colorectal cancer (mCRC): Results from a large Czech observational registry (CSTP). Proc Am Soc Clin Oncol Gastrointest Cancer Symp 2010, Abstr 467
37.
Zurück zum Zitat Nalluri SR, Chu D, Keresztes R et al (2008) Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 300(19):2277–2285PubMedCrossRef Nalluri SR, Chu D, Keresztes R et al (2008) Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 300(19):2277–2285PubMedCrossRef
38.
Zurück zum Zitat Hurwitz HI, Saltz LB, Van Cutsem E et al (2011) Venous thromboembolic events with chemotherapy plus bevacizumab: a pooled analysis of patients in randomized phase II and III studies. J Clin Oncol 13:1757–1764CrossRef Hurwitz HI, Saltz LB, Van Cutsem E et al (2011) Venous thromboembolic events with chemotherapy plus bevacizumab: a pooled analysis of patients in randomized phase II and III studies. J Clin Oncol 13:1757–1764CrossRef
39.
Zurück zum Zitat Scappaticci FA, Skillings JR, Holden SN et al (2007) Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst 99(16):1232–1239PubMedCrossRef Scappaticci FA, Skillings JR, Holden SN et al (2007) Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst 99(16):1232–1239PubMedCrossRef
40.
Zurück zum Zitat Ranpura V, Hapani S, Chuang J, Wu S (2010) Risk of cardiac ischemia and arterial thromboembolic events with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis of randomized controlled trials. Acta Oncol 49(3):287–297PubMedCrossRef Ranpura V, Hapani S, Chuang J, Wu S (2010) Risk of cardiac ischemia and arterial thromboembolic events with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis of randomized controlled trials. Acta Oncol 49(3):287–297PubMedCrossRef
Metadaten
Titel
Targeted agents: review of toxicity in the elderly metastatic colorectal cancer patients
verfasst von
Flora Kyriakou
Panteleimon Kountourakis
Demetris Papamichael
Publikationsdatum
01.12.2011
Verlag
Springer-Verlag
Erschienen in
Targeted Oncology / Ausgabe 4/2011
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-011-0198-1

Weitere Artikel der Ausgabe 4/2011

Targeted Oncology 4/2011 Zur Ausgabe

Positiver FIT: Die Ursache liegt nicht immer im Dickdarm

27.05.2024 Blut im Stuhl Nachrichten

Immunchemischer Stuhltest positiv, Koloskopie negativ – in solchen Fällen kann die Blutungsquelle auch weiter proximal sitzen. Ein Forschungsteam hat nachgesehen, wie häufig und in welchen Lokalisationen das der Fall ist.

Mammakarzinom: Brustdichte beeinflusst rezidivfreies Überleben

26.05.2024 Mammakarzinom Nachrichten

Frauen, die zum Zeitpunkt der Brustkrebsdiagnose eine hohe mammografische Brustdichte aufweisen, haben ein erhöhtes Risiko für ein baldiges Rezidiv, legen neue Daten nahe.

Mehr Lebenszeit mit Abemaciclib bei fortgeschrittenem Brustkrebs?

24.05.2024 Mammakarzinom Nachrichten

In der MONARCHE-3-Studie lebten Frauen mit fortgeschrittenem Hormonrezeptor-positivem, HER2-negativem Brustkrebs länger, wenn sie zusätzlich zu einem nicht steroidalen Aromatasehemmer mit Abemaciclib behandelt wurden; allerdings verfehlte der numerische Zugewinn die statistische Signifikanz.

ADT zur Radiatio nach Prostatektomie: Wenn, dann wohl länger

24.05.2024 Prostatakarzinom Nachrichten

Welchen Nutzen es trägt, wenn die Strahlentherapie nach radikaler Prostatektomie um eine Androgendeprivation ergänzt wird, hat die RADICALS-HD-Studie untersucht. Nun liegen die Ergebnisse vor. Sie sprechen für länger dauernden Hormonentzug.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.