Zusammenfassung
Das Nierenzellkarzinom ist das dritthäufigste und nach wie vor
tödlichste urologische Malignom; seine Inzidenz ist in den letzten 40
Jahren signifikant angestiegen. Etwa jeder zweite Patient entwickelt entweder
zeitnah zur Primärdiagnose oder metachron Metastasen seiner
Tumorerkrankung. Durch das zunehmende Verständnis genetischer Alterationen
bzw. dysfunktionaler Signaltransduktionswege der verschiedenen
Nierenzellkarzinomsubtypen wurde in den letzten Jahren die Entwicklung von
innovativen zielgerichteten Therapeutika möglich. Mit Hilfe dieser
Substanzen, die insbesondere den VEGF- und mTOR-Signaltransduktionsweg
blockieren, wurden die Behandlungsstrategien des fortgeschrittenen
Nierenzellkarzinoms revolutioniert, das mittlere Gesamtüberleben hat sich
innerhalb weniger Jahre mindestens verdoppelt. Dieser Übersichtsartikel
diskutiert die derzeit aktuellen klinischen Studienergebnisse zu den zur
Verfügung stehenden Substanzen, die Wertigkeit ihres präoperativen,
adjuvanten, sequenziellen und kombinierten Einsatzes.
Summary
Renal cell carcinoma (RCC) is a common urologic tumour and accounts
for about 3 % of all human malignancies; its incidence has
increased steadily in recent decades. The annual mortality-to-incidence ratio
with RCC is significantly higher compared to other urological malignancies. It
is estimated that approximately 25–30 % of all patients
with RCC have metastases at presentation, and even following complete resection
of the primary tumour by radical or partial nephrectomy, relapse occurs in
20–30 % of patients. Only recently, the discovery of
specific genetic alterations as well as distinct dysfunctional signal
transduction pathways in the different renal cell carcinoma subtypes has
enabled the development of innovative targeted drugs. Particularly those
targeting the VEGF- and mTOR-pathways revolutionized the treatment of advanced
renal cancer; in fact, the median tumour specific overall survival could be at
least doubled in only a few years. This review discusses current data on
clinical trials evaluating these innovative drugs with focus on their efficacy
in the adjuvant and neoadjuvant setting as well as their sequential and
combined application.
Schlüsselwörter
Nierenzellkarzinom - zielgerichtete Therapie - Nephrektomie - Metastasen - adjuvante
Therapie
Keywords
renal cell carcinoma - target therapy - nephrectomy - metastasis - adjuvant therapy
Literatur
- 01
Aitchison M, Bray C, van Poppel H, Sylvester R, Graham J, Innes C, McMahon L, Vasey P A.
Preliminary results from a randomized phase III trial of
adjuvant interleukin-2, interferon alpha and 5-fluorouracil in patients with
a
high risk of relapse after nephrectomy for renal cell carcinoma (RCC).
J Clin Oncol.
2008;
26
- 02
Amato R J, Harris P, Dalton M, Khan M, Alter R, Zhai Q, Brady J R, Jac J, Hauke R,
Srinivas S.
A phase II trial of intra-patient dose-escalated sorafenib in
patients (pts) with metastatic renal cell cancer (MRCC).
J Clin Oncol.
2007;
25
- 03 ARISER-Trial .A randomized double blind phase III study to evaluate
adjuvant cG250 treatment versus placebo in patients with clear cell RCC and
high risk of recurrence. Protocol WX-2003-07-HR http://www.ariserstudy.com
- 04
Atzpodien J, Schmitt E, Gertenbach U, Fornara P, Heynemann H, Maskow A, Ecke M, Woltjen H H,
Jentsch H, Wieland W, Wandert T, Reitz M.
Adjuvant treatment with interleukin-2- and
interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour
nephrectomy: results of a prospectively randomised trial of the German
Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).
Br J Cancer.
2005;
92
843-846
- 05
Barbastefano J, Garcia J A, Elson P, Wood L S, Lane B S, Dreicer R, Campbell S, Rini B I.
Association of percentage of tumor burden removed with
debulking nephrectomy and progression-free survival (PFS) in metastatic renal
cell carcinoma (mRCC) patients (Pts) treated with VEGF-targeted therapy.
J Clin Oncol.
2009;
27
- 06
Beck J, Bajetta E, Escudier B, Negrier S, Keilholz U, Szczylik C, Mersmann S, Burock K,
Erlandsson F, Huber C. investigators .
ftE-As. A large open-label, non-comparative, phase III study
of the multi-targeted kinase inhibitor Sorafenib in European patients with
advanced renal cell carcinoma.
Eur J Cancer.
2007;
5
(S 300)
- 07
Bracarda S, Porta C, Boni C, Santoro A, Artioli F, di Bartolomeo C, Contu A, Gasparro D,
de Angelis V, Caserta C, Group G S.
Randomized prospective phase II trial of two schedules of
sorafenib daily and interferon-a2a (IFN) in metastatic renal cell carcinoma
(RAPSODY): GOIRC Study 0681.
J Clin Oncol.
2007;
25
- 08
Choi H, Charnsangavej C, Faria S C, Macapinlac H A, Burgess M A, Patel S R, Chen L L,
Podoloff D A, Benjamin R S.
Correlation of computed tomography and positron emission
tomography in patients with metastatic gastrointestinal stromal tumor treated
at a single institution with imatinib mesylate: proposal of new computed
tomography response criteria.
J Clin Oncol.
2007;
25
1753-1759
- 09 Choueiri T K, Brick A J, McDermott D, Clement J, Kwabi C, Shah K, Chen K, Duh M S,
Neary M P, Oh W K. Treatment and dosing patterns for angiogenesis inhibitor
therapies in patietns with metastatic renal cell carcinoma (MRCC). ESMO Meeting:
abstract 593 2008
- 10
Clark J I, Atkins M B, Urba W J, Creech S, Figlin R A, Dutcher J P, Flaherty L, Sosman J A,
Logan T F, White R, Weiss G R, Redman B G, Tretter C P, McDermott D, Smith J W, Gordon M S,
Margolin K A.
Adjuvant high-dose bolus interleukin-2 for patients with
high-risk renal cell carcinoma: a cytokine working group randomized trial.
J Clin Oncol.
2003;
21
3133-3140
- 11
Cross M J, Dixelius J, Matsumoto T, Claesson-Welsh L.
VEGF-receptor signal transduction.
Trends Biochem Sci.
2003;
28
488-494
- 12
Dham A, Dudek A Z.
Sequential therapy with sorafenib and sunitinib in renal cell
carcinoma.
J Clin Oncol.
2007;
25
- 13
Doehn C, Richter A, Theodor R, Lehmacher W, Jocham D.
Eine adjuvante Vakzinierung mit Reniale verlängert das
progressionsfreie Überleben und das Gesamtüberleben bei Patienten mit
einem Nierenzellkarzinom nach radikaler Nephrektomie: Zweite Analyse einer
randomisierten Phase-III Studie.
Urologe.
2006;
45
S113
- 14
Drabkin H A, Figlin R A, Stadler W M, Hutson T E, Hajdenberg J, Chu L, Trent D, Campos L T,
Kelly F, Bukowski R M. investigators obotA .
The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) expanded
access trial: Safety and efficacy in patients (pts) with prior bevacizumab
(BEV) treatment.
J Clin Oncol.
2007;
25
- 15
Dudek A Z, Zolnierek J, Dham A, Lindgren B R, Szczylik C.
Sequential therapy with sorafenib and sunitinib in renal cell
carcinoma.
Cancer.
2009;
115
61-67
- 16
Dutcher J P, Szczylik C, Tannir N, Benedetto P, Ruff P, Hsu A, Berkenblit A, Thiele A,
Strahs A, Feingold J.
Correlation of survival with tumor histology, age, and
prognostic risk group for previously untreated patients with advanced renal
cell carcinoma (adv RCC) receiving temsirolimus (TEMSR) or interferon-alpha
(IFN).
Clin Oncol.
2007;
25
- 17
Dutcher J P, Wilding G, Hudes G R, Stadler W M, Kim S, Tarazi Jc, Rosbrook B, Rini B I.
Sequential axitinib (AG-013736) therapy of patients (pts)
with metastatic clear cell renal cell cancer (RCC) refractory to sunitinib and
sorafenib, cytokines and sorafenib, or sorafenib alone.
J Clin Oncol.
2008;
26
- 18 ECOG-E2805 A randomized, double-blind phase III trial of
adjuvant sunitinib versus sorafenib versus placebo in patients with resected
renal cell carcinoma (ASSURE-Trial). http://www.cancer.gov/clinicaltrials/ft-ECOG-E2805
- 19
Eichelberg C, Heuer R, Chun F K, Hinrichs K, Zacharias M, Huland H, Heinzer H.
Sequential use of the tyrosine kinase inhibitors sorafenib
and sunitinib in metastatic renal cell carcinoma: a retrospective outcome
analysis.
Eur Urol.
2008;
54
1373-1378
- 20
Eisenhauer E A, Therasse P, Bogaerts J, Schwartz L H, Sargent D, Ford R, Dancey J,
Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D,
Verweij J.
New response evaluation criteria in solid tumours: revised
RECIST guideline (version 1.1).
Eur J Cancer.
2009;
45
228-247
- 21
Escudier B, Eisen T, Stadler W M, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C,
Solska E, Desai A A, Rolland F, Demkow T, Hutson T E, Gore M, Freeman S, Schwartz B,
Shan M, Simantov R, Bukowski R M.
Sorafenib in advanced clear-cell renal-cell carcinoma.
N Engl J Med.
2007;
356
125-134
- 22
Escudier B, Koralewski P, Pluzanska A, Ravaud A, Bracarda S, Szczylik C, Chevreau C,
Filipek M, Melichar B, Moore N. investigators. obotA .
A randomized, controlled, double-blind phase III study
(AVOREN) of bevacizumab/interferon-a2a vs placebo/interferon- a2a as first-line
therapy in metastatic renal cell carcinoma.
J Clin Oncol.
2007;
25
- 23
Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, Chevreau C,
Filipek M, Melichar B, Bajetta E, Gorbunova V, Bay J O, Bodrogi I, Jagiello-Gruszfeld A,
Moore N.
Bevacizumab plus interferon alfa-2a for treatment of
metastatic renal cell carcinoma: a randomised, double-blind phase III
trial.
Lancet.
2007;
370
2103-2111
- 24 Escudier B, Ravaud A, Oudard S, Porta C, Hutson T, Bracarda S, Figlin R, Thompson J,
Grünwald V, Hollaender N, Urbanowitz G, Kay A, Motzer R. Group ftR-S .Phase-3 Randomized
Trial of Everolimus (RAD001) vs Placebo in
Metastatic Renal Cell Carcinoma. ESMO Meeting: abstract 720 2008
- 25
Escudier B J, Bellmunt J, Negrier S, Melichar B, Bracarda S, Ravaud A, Golding S,
Jethwa S.
Final results of the phase III, randomized, double-blind
AVOREN trial of first-line bevacizumab
(BEV) + interferon-α2a (IFN) in metastatic renal cell
carcinoma (mRCC).
J Clin Oncol.
2009;
27
- 26
Escudier B J, Ravaud A, Négrier S, Szczylik C, Bellmunt Molins J, Bracarda S, Pisa P,
Gaudreault J, Bajetta E.
Update on AVOREN trial in metastatic renal cell carcinoma
(mRCC): Efficacy and safety in subgroups of patients (pts) and pharmacokinetic
(PK) analysis.
J Clin Oncol.
2008;
26
- 27
Feldman D R, Kondagunta G V, Ronnen E A, Fischer P, Chang R, Baum M, Ginsberg M S,
Ishill N, Patil S, Motzer R J.
Phase I trial of bevacizumab plus sunitinib in patients (pts)
with metastatic renal cell carcinoma (mRCC).
J Clin Oncol.
2007;
25
- 28
Fischer P, Patel P, Carducci M A, McDermott D F, Hudes G R, Lubiniecki G M, Gelder M S,
Senico P, Curiel R E, Motzer R J.
Phase I study combining treatment with temsirolimus and
sunitinib malate in patients with advanced renal cell carcinoma.
J Clin Oncol.
2008;
26
- 29
Flanigan R C, Mickisch G, Sylvester R, Tangen C, Van Poppel H, Crawford E D.
Cytoreductive nephrectomy in patients with metastatic renal
cancer: a combined analysis.
J Urol.
2004;
171
1071-1076
- 30
Flanigan R C, Salmon S E, Blumenstein B A, Bearman S I, Roy V, McGrath P C, Caton Jr J R,
Munshi N, Crawford E D.
Nephrectomy followed by interferon alfa-2b compared with
interferon alfa-2b alone for metastatic renal-cell cancer.
N Engl J Med.
2001;
345
1655-1659
- 31
George D J, Michaelson M D, Rosenberg J E, Bukowski R M, Sosman J A, Stadler W M,
Margolin K, Hutson T E, Rini B I.
Phase II trial of sunitinib in bevacizumab-refractory
metastatic renal cell carcinoma (mRCC): Updated results and analysis of
circulating biomarkers.
J Clin Oncol.
2007;
25
- 32
Gollob J A, Rathmell W K, Richmond T M, Marino C B, Miller E K, Grigson G, Watkins C,
Gu L, Peterson B L, Wright J J.
Phase II trial of sorafenib plus interferon alfa-2b as first-
or second-line therapy in patients with metastatic renal cell cancer.
J Clin Oncol.
2007;
25
3288-3295
- 33
Gore M E, Porta C, Oudard S, Bjarnason G, Castellano D, Szczylik C, Mainwaring P N,
Schöffski P, Rini B I, Bukowski R M.
Sunitinib in metastatic renal cell carcinoma (mRCC):
Preliminary assessment of toxicity in an expanded access trial with
subpopulation analysis.
J Clin Oncol.
2007;
25
- 34
Heng D Y, Xie W, Regan M M, Cheng T, North S, Knox J J, Kollmannsberger C, McDermott D,
Rini B I, Choueiri T K.
Prognostic factors for overall survival (OS) in patients with
metastatic renal cell carcinoma (RCC) treated with vascular endothelial growth
factor (VEGF)-targeted agents: Results from a large multicenter study.
J Clin Oncol.
2009;
27
- 35
Houk B E, Bello C L, Michaelson M D, Bukowski R M, Redman B G, Hudes G R, Wilding G,
Motzer R J.
Exposure-response of sunitinib in metastatic renal cell
carcinoma (mRCC): A population pharmacokinetic/pharmacodynamic (PKPD)
approach.
J Clin Oncol.
2007;
25
- 36
Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J,
McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf I G, Barbarash O, Gokmen E,
O'Toole T, Lustgarten S, Moore L, Motzer R J.
Temsirolimus, interferon alfa, or both for advanced
renal-cell carcinoma.
N Engl J Med.
2007;
356
2271-2281
- 37
Jac J, Amato R J, Giessinger S, Saxena S, Willis J P.
A phase II study with a daily regimen of the oral mTOR
inhibitor RAD001 (everolimus) in patients with metastatic renal cell carcinoma
which has progressed on tyrosine kinase inhibition therapy.
J Clin Oncol.
2008;
26
- 38
Jac J, Giessinger S, Khan M, Willis J, Chiang S, Amato R.
A phase II trial of RAD001 in patients (Pts) with metastatic
renal cell carcinoma (MRCC).
J Clin Oncol.
2007;
25
- 39
Jocham D, Richter A, Hoffmann L, Iwig K, Fahlenkamp D, Zakrzewski G, Schmitt E, Dannenberg T,
Lehmacher W, Wietersheim J. von, Doehn C.
Adjuvant autologous renal tumour cell vaccine and risk of
tumour progression in patients with renal-cell carcinoma after radical
nephrectomy: phase III, randomised controlled trial.
Lancet.
2004;
363
594-599
- 40
Jonasch E, Tsavachdidou D, Wood C G, Matin S F, Corn P G, Tamboli P, Wang X, Tannir N.
Phase II presurgical study of bevacizumab plus erlotinib in
untreated patients with metastatic renal cell carcinoma.
J Clin Oncol.
2009;
27
- 41
Kondagunta G V, Hudes G R, Figlin R, Wilding G, Hariharan S, Kempin S N, Fayyad R,
Hoosen S, Motzer R J.
Sunitinib malate (SU) plus interferon (IFN) in first line
metastatic renal cell cancer (mRCC): Results of a dose-finding study.
J Clin Oncol.
2007;
25
- 42
Liu Z, Burke J, Zheng J, Johnson J.
Survival and association with time to treatment change in
patients with metastatic renal cell carcinoma.
J Clin Oncol.
2009;
27
- 43
Logan T, McDermott D F, Dutcher J P, Makhson A, Mikulas J, Berkenblit A, Galand L,
Krygowski M, Hudes G R.
Exploratory analysis of the influence of nephrectomy status
on temsirolimus efficacy in patients with advanced renal cell carcinoma and
poor-risk features.
J Clin Oncol.
2008;
26
- 44
Mancuso A P, Donato De Paola E, Catalano A, Calabrò F, Messina C, Zivi A, Cerbone L,
Vigna L, Caristo R, Sternberg C N.
Phase II dose escalation study of sorafenib in patients with
metastatic renal cell carcinoma (mRCC) who have had prior treatment with
VEGFR-TKI antiangiogenic treatment.
J Clin Oncol.
2009;
27
- 45
Messing E M, Manola J, Wilding G, Propert K, Fleischmann J, Crawford E D, Pontes J E,
Hahn R, Trump D.
Phase III study of interferon alfa-NL as adjuvant treatment
for resectable renal cell carcinoma: an Eastern Cooperative Oncology
Group/Intergroup trial.
J Clin Oncol.
2003;
21
1214-1222
- 46
Mickisch G H, Garin A, van Poppel H, de Prijck L, Sylvester R.
Radical nephrectomy plus interferon-alfa-based immunotherapy
compared with interferon alfa alone in metastatic renal-cell carcinoma: a
randomised trial.
Lancet.
2001;
358
966-970
- 47
Motzer R J, Escudier B, Oudard S, Porta C, Hutson T E, Bracarda S, Hollaender N, Urbanowitz G,
Kay A, Ravaud A.
RAD001 vs placebo in patients with metastatic renal cell
carcinoma (RCC) after progression on VEGFr-TKI therapy: Results from a
randomized, double-blind, multicenter Phase-III study.
J Clin Oncol.
2008;
26
- 48
Motzer R J, Figlin R A, Hutson T E, Tomczak P, Bukowski R M, Rixe O, Bjarnason G A,
Kim S T, Chen I, Michaelson D.
Sunitinib versus interferon-alfa (IFN-a) as first-line
treatment of metastatic renal cell carcinoma (mRCC): Updated results and
analysis of prognostic factors.
J Clin Oncol.
2007;
25
- 49
Motzer R J, Hutson T E, Tomczak P, Michaelson M D, Bukowski R M, Rixe O, Oudard S,
Negrier C, Szczylik C, Kim S T, Chen I, Bycott P W, Baum C M, Figlin R A.
Sunitinib versus interferon alfa in metastatic renal-cell
carcinoma.
N Engl J Med.
2007;
356
115-124
- 50
Nathan P D, Vinayan A, Stott D, Goh V.
CT response assessment combining reduction in size and
arterial enhancement correlates with time to progression in metastatic renal
cancer patients treated with TKIs.
J Clin Oncol.
2009;
27
- 51
Passalacqua R, Buzio C, Buti S, Labianca R, Porta C, Boni C, Rondini E, Camisa R,
Sabbatini R, Artioli F, Caminiti C.
Adjuvant low-dose interleukin-2 (IL2) plus interferone-alpha
(IFN) in operable renal cell cancer (RCC). A phase III, randomized,
multicenter, independent trial of the Italian Oncology Group for Clinical
Research (GOIRC).
J Clin Oncol.
2007;
25
- 52
Patil S, Figlin R A, Hutson T E, Michaelson M D, Négrier S, Kim S T, Huang X, Motzer R J.
Prognostic factors for overall survival with sunitinib as
first-line therapy in patients with metastatic renal cell carcinoma
(mRCC).
J Clin Oncol.
2009;
27
- 53
Pizzocaro G, Piva L, Colavita M, Ferri S, Artusi R, Boracchi P, Parmiani G, Marubini E.
Interferon adjuvant to radical nephrectomy in Robson stages
II and III renal cell carcinoma: a multicentric randomized study.
J Clin Oncol.
2001;
19
425-431
- 54 Porta C, Procopio G, Sabbatini R, Bearz A, Chiappino I, Imarisio I, Guadalupi V,
Paglino C, Verzoni E, Ferraris E, Bajetta E. Retrospective Analysis of the Sequential
Use of Sorafenib and
Sunitinib in Patients with Advanced Renal Cell Carcinoma (RCC). EAU Annual Meeting:
abstract 252 2009
- 55
Richey S L, Culp S H, Wood C G, Corn P G, Jonasch E, Tannir N M.
Outcome of patients (pts) with metastatic renal cell
carcinoma (mRCC) treated with systemic therapy without cytoreductive
nephrectomy (CN).
J Clin Oncol.
2009;
27
- 56
Rini B I, Halabi S, Rosenberg J, Stadler W M, Vaena D A, Atkins J N, Picus J, Czaykowski P,
Dutcher J, Small E J.
Bevacizumab plus interferon-alpha versus interferon-alpha
monotherapy in patients with metastatic renal cell carcinoma: Results of
overall survival for CALGB 90206.
J Clin Oncol.
2009;
27
- 57
Rini B I, Small E J.
Biology and clinical development of vascular endothelial
growth factor-targeted therapy in renal cell carcinoma.
J Clin Oncol.
2005;
23
1028-1043
- 58
Rini B I, Tamaskar I, Shaheen P, Salas R, Garcia J, Wood L, Reddy S, Dreicer R, Bukowski R M.
Hypothyroidism in patients with metastatic renal cell
carcinoma treated with sunitinib.
J Natl Cancer Inst.
2007;
99
81-83
- 59
Rini B I, Wilding G T, Hudes G, Stadler W M, Kim S, Tarazi J C, Bycott P W, Liau K F,
Dutcher J P.
Axitinib (AG-013736; AG) in patients (pts) with metastatic
renal cell cancer (RCC) refractory to sorafenib.
J Clin Oncol.
2007;
25
- 60
Rosenberg J E, Weinberg V K, Claros C, Ryan C, Lin M A, Fong L, Brocks D, Small E J.
Phase I study of sorafenib and RAD001 for metastatic clear
cell renal cell carcinoma.
J Clin Oncol.
2008;
26
- 61
Ryan C W, Goldman B H, Lara Jr P N, Mack P C, Beer T M, Tangen C M, Lemmon D, Pan C X,
Drabkin H A, Crawford E D.
Sorafenib with interferon alfa-2b as first-line treatment of
advanced renal carcinoma: a phase II study of the Southwest Oncology
Group.
J Clin Oncol.
2007;
25
3296-3301
- 62
Sablin M P, Bouaita L, Balleyguier C, Gautier J, Celier C, Balcaceres J L, Oudard S,
Ravaud A, Négrier S, Escudier B.
Sequential use of sorafenib and sunitinib in renal cancer:
Retrospective analysis in 90 patients.
J Clin Oncol.
2007;
25
- 63
Schmidinger M, Vogl U M, Lamm W, Bojic M, Bojic A, Zielinski C C.
Temsirolimus in heavily pretreated patients with metastatic
renal cell carcinoma: Preliminary results from the Austrian Compassionate Use
Program.
J Clin Oncol.
2008;
26
- 64
Speca J C, Mears A L, Creel P A, Yenser S E, Bendell J C, Morse M A, Hurwitz H I,
Armstrong A J, George D J.
Phase I study of PTK787/ZK222584 (PTK/ZK) and RAD001 for
patients with advanced solid tumors and dose expansion in renal cell carcinoma
patients.
J Clin Oncol.
2007;
25
- 65
Stadler W M, Figlin R A, Ernstoff M S, Curti B, Pendergrass K, Srinivas S, Canfield V,
Weissman C, Poulin-Costello M, Bukowski R M. investigators. obotA .
The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) expanded
access trial: Safety and efficacy in patients (pts) with non-clear cell (NCC)
renal cell carcinoma (RCC).
J Clin Oncol.
2007;
25.
- 66
Staehler M, Haseke N, Schöppler G, Stadler T, Stief C G.
Sorafenib (Nexavar) beim metastasierten sarkomatoiden
Nierenzellkarzinom nach Versagen einer vorangegangenen Chemotherapie mit
Doxorubicin und Gemcitabine.
J Urol Urogyn.
2007;
14
- 67 Staehler M, Haseke N, Stadler T, Zilinberg K, Nordhaus C, Dieckmann M, Nuhn P,
Stief C G. Intraindividuelle Dosis-Eskalation mit Sorafenib zu Therapie
des metastasierten klarzelligem Nierenzellkarzinom (mRCC). 61. Kongress der
Deutschen Gesellschaft für
Urologie (DGU): abstract P 6.10 2009
- 68 Staehler M, Procopio G, Keilholz U, Negrier S, Szczylik C, Beck J, Strauss U P,
Burock K, Escudier B. A subanalysis of patients with and without prior nephrectomy
in a large open-label, non-comparative phase III European Advanced Renal Cell
Carcinoma (RCC) Sorafenib Study (EU-ARCCS). 61. Kongress der deutschen Gesellschaft
für
Urologie (DGU): abstract V 4.6 2009
- 69
Szczylik C, Demkow T, Staehler M, Rolland F, Negrier S, Hutson T E, Bukowski R M,
Scheuring U J, Burk K, Escudier B.
Randomized phase II trial of first-line treatment with
sorafenib versus interferon in patients with advanced renal cell carcinoma:
Final results.
J Clin Oncol.
2007;
25
- 70
Szczylik C, Porta C, Bracarda S, Hawkins R, Bjarnason G A, Oudard S, Lee S, Carteni G,
Hariharan S, Gore M E.
Sunitinib in patients with or without prior nephrectomy (Nx)
in an expanded access trial of metastatic renal cell carcinoma (mRCC).
J Clin Oncol.
2008;
26
- 71
Tamaskar I, Garcia J A, Elson P, Wood L, Mekhail T, Dreicer R, Rini B I, Bukowski R M.
Antitumor effects of sunitinib or sorafenib in patients with
metastatic renal cell carcinoma who received prior antiangiogenic therapy.
J Urol.
2008;
179
81-86
- 72
Tannir N, Wong Y, Kollmannsberger C, Ernstoff M S, Perry D J, Appleman L J, Posadas E,
Qian J, Ricker J L, Michaelson D M.
Phase II trial of ABT-869 in advanced renal cell cancer (RCC)
after sunitinib failure: Efficacy and safety results.
J Clin Oncol.
2009;
27
- 73
Unnithan J S, Choueiri T, Garcia J, Dreicer R, Laura W, Bukowski R, Rini B.
Safety of VEGF-targeted tyrosine kinase inhibitors in
patients (Pts) with metastatic renal cell carcinoma (mRCC) and central nervous
system (CNS) metastases.
J Clin Oncol.
2007;
25
- 74
van der Veldt A, Meijerink M R, van den Eertwegh A J, Haanen J B, Boven E.
Choi response criteria for prediction of clinical outcome in
patients with metastatic renal cell cancer treated with sunitinib.
J Clin Oncol.
2009;
27
- 75
Vickers M M, Choueiri T K, Zama I, Cheng T, North S, Knox J J, Kollmannsberger C,
McDermott D F, Rini B I, Heng D Y.
Failure of initial VEGF-targeted therapy in metastatic renal
cell carcinoma (mRCC): What next?.
J Clin Oncol.
2009;
27
- 76
Whorf R C, Hainsworth J D, Spigel D R, Yardley D A, Burris H A, Waterhouse D M, Vazquez E R,
Greco F A.
Phase II study of bevacizumab and everolimus (RAD001) in the
treatment of advanced renal cell carcinoma (RCC).
J Clin Oncol.
2008;
26
- 77
Wolter P, Stefan C, Decallonne B, Dumez H, Fieuws S, Wildiers H, Clement P, Debaere D,
van Oosterom A, Schöffski P.
Evaluation of thyroid dysfunction as a candidate surrogate
marker for efficacy of sunitinib in patients (pts) with advanced renal cell
cancer (RCC).
J Clin Oncol.
2008;
26
- 78
Wood L, Bukowski R M, Dreicer R, Elson P, Garcia J A, Gilligan T, Mekhail T, Rini B I.
Temsirolimus (TEM) in metastatic renal cell carcinoma (mRCC):
Safety and efficacy in patients (pts) previously treated with VEGF-targeted
therapy.
J Clin Oncol.
2008;
26
- 79
Wood L, Garcia J A, Elson P, Salas R N, Lane B R, Klein E, Stephenson A, Dreicer R,
Campbell S C, Rini B I.
Sunitinib in patients (pts) with unresectable primary renal
cell carcinoma (RCC).
J Clin Oncol.
2009;
27
- 80
Zimmermann K, Schmittel A, Steiner U, Asemissen A M, Knoedler M, Thiel E, Miller K,
Keilholz U.
Sunitinib treatment for patients with advanced clear-cell
renal-cell carcinoma after progression on sorafenib.
Oncology.
2009;
76
350-354
Korrespondenzadresse
Prof. Dr. med. Andres Jan Schrader
Klinik für Urologie und
Kinderurologie
Philipps-Universität Marburg
Baldingerstrasse
35043 Marburg
Email: ajschrader@gmx.de
