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Aktuelle Urol 2008; 39(6): 429-434
DOI: 10.1055/s-2008-1038284
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Testikuläre Keimzelltumoren – Erklärungsmodelle für die hohe Ansprechrate auf Cisplatin-basierte Chemotherapien und neue Therapieoptionen

Testicular Cancer – Explanatory Models for high Cisplatin Chemosensibility and new Therapeutic OptionsJ.  Ebbing1 , F.  Christoph1 , C.  Kempkensteffen1 , S.  Weikert1 , M.  Schostak1 , S.  Hinz1 , M.  Lein1 , K.  Miller1 , M.  Schrader1
  • 1Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin
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Publikationsverlauf

Publikationsdatum:
31. Oktober 2008 (online)

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Zusammenfassung

Dieser Artikel bietet eine Übersicht über die aktuelle Datenlage bei Chemotherapien von Keimzelltumoren. Neben einer kurzen Vorstellung der leitliniengerechten Standardchemotherapie von Keimzelltumoren haben sich die Autoren mit der Frage beschäftigt, warum Keimzelltumoren eine überaus hohe Chemosensibilität im Vergleich zu anderen Tumorentitäten aufweisen. Des Weiteren wird die aktuelle Datenlage zu alternativen Chemotherapien sowie zu molekularen, molekulargenetischen und pharmakogenetischen Therapiekonzepten beleuchtet. Datengrundlage war eine Recherche in MEDLINE der Pubmed-Datenbank.

Abstract

This article offers a review about the current facts of chemotherapy in testicular cancer. Besides a short presentation of the guideline-standard therapy the authors deal with the question as to why testicular cancer shows an extraordinarily high chemosensibility compared to other tumours. Furthermore, the current data on alternative chemotherapies as well as of molecular, molecular-genetic and pharmacogenetic therapeutic concepts are explored. Data were obtained from researches in Medline of the Pubmed database.

Schlüsselwörter

Bleomycin-Hydrolase-Polymorphismus - Chemosensibilität - Cisplatin-Resistenz - Excision Repair Cross Complementing 1 (ERCC1)-Faktor - GOP - Keimzelltumoren - molekulare Therapieoptionen - Nukleotid-Exzisions-Reparatur (NER) - Polychemotherapie

Key words

bleomycin hydrolase polymorphism - chemosensibility - cisplatin resistance - excision repair cross complementing 1 (ERCC1) factor - GOP - molecular therapeutic options - nucleotide excision repair (NER) - polychemotherapy - testicular cancer

Literatur

  • 1 International Germ Cell Consensus Classification . A prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group.  J Clin Oncol. 1997;  15 594-603
    Suche in Google Scholar
  • 2 Arriola E L, Rodriguez-Lopez A M, Hickman J A. et al . Bcl-2 overexpression results in reciprocal downregulation of Bcl-X(L) and sensitizes human testicular germ cell tumours to chemotherapy-induced apoptosis.  Oncogene. 1999;  18 1457-1464
    Suche in Google Scholar
  • 3 Becker N, Wahrendorf J. Krebsatlas der Bundesrepublik Deutschland/Atlas of cancer mortality in Germany. 3ed. Berlin, Heidelberg, New York: Springer 1998
    Suche in Google Scholar
  • 4 Bellmunt J, Paz-Ares L, Cuello M. et al . Gene expression of ERCC1 as a novel prognostic marker in advanced bladder cancer patients receiving cisplatin-based chemotherapy.  Ann Oncol. 2007;  18 522-528
    Suche in Google Scholar
  • 5 Bokemeyer C. Bleomycin in testicular cancer: will pharmacogenomics improve treatment regimens?.  J Clin Oncol. 2008;  26 1783-1785
    Suche in Google Scholar
  • 6 Bokemeyer C, Oechsle K, Honecker F. et al . Combination chemotherapy with gemcitabine, oxaliplatin, and paclitaxel in patients with cisplatin-refractory or multiply relapsed germ-cell tumors: a study of the German Testicular Cancer Study Group.  Ann Oncol. 2008;  19 448-453
    Suche in Google Scholar
  • 7 Bokemeyer C, Beyer J, Metzner B. et al . Phase II study of paclitaxel in patients with relapsed or cisplatin-refractory testicular cancer.  Ann Oncol. 1996;  7 31-34
    Suche in Google Scholar
  • 8 Bokemeyer C, Gerl A, Schoffski P. et al . Gemcitabine in patients with relapsed or cisplatin-refractory testicular cancer.  J Clin Oncol. 1999;  17 512-516
    Suche in Google Scholar
  • 9 Braun R E. Every sperm is sacred – or is it?.  Nat Genet. 1998;  18 202-204
    Suche in Google Scholar
  • 10 Bray F, Richiardi L, Ekbom A. et al . Trends in testicular cancer incidence and mortality in 22 European countries: continuing increases in incidence and declines in mortality.  Int J Cancer. 2006;  118 3099-3111
    Suche in Google Scholar
  • 11 Chew S L, Baginsky L, Eperon I C. An exonic splicing silencer in the testes-specific DNA ligase III beta exon.  Nucleic acids research. 2000;  28 402-410
    Suche in Google Scholar
  • 12 Chresta C M, Masters J R, Hickman J A. Hypersensitivity of human testicular tumors to etoposide-induced apoptosis is associated with functional p53 and a high Bax:Bcl-2 ratio.  Cancer Res. 1996;  56 1834-1841
    Suche in Google Scholar
  • 13 Cleaver J E, Karplus K, Kashani-Sabet M. et al . Nucleotide excision repair “a legacy of creativity”.  Mutation research. 2001;  485 23-36
    Suche in Google Scholar
  • 14 Bajorin D F, Nichols C R, Margolin K A. et al . Phase III trial of conventional-dose chemotherapy alone or with high-dose chemotherapy for metastatic germ cell tumors (GCT) patients (PTS): A cooperative group trial by Memorial Sloan-Kettering Cancer Center, ECOG, SWOG, and CALGB.  JCO. 2006;  24 4510
    Suche in Google Scholar
  • 15 de Haas E C, Zwart N, Meijer C. et al . Variation in bleomycin hydrolase gene is associated with reduced survival after chemotherapy for testicular germ cell cancer.  J Clin Oncol. 2008;  26 1817-1823
    Suche in Google Scholar
  • 16 de Wit R, Louwerens M, de Mulder P H. et al . Management of intermediate-prognosis germ-cell cancer: results of a phase I/II study of Taxol-BEP.  Int J Cancer. 1999;  83 831-833
    Suche in Google Scholar
  • 17 Dunn T A, Schmoll H J, Grunwald V. et al . Comparative cytotoxicity of oxaliplatin and cisplatin in non-seminomatous germ cell cancer cell lines.  Invest New Drugs. 1997;  15 109-114
    Suche in Google Scholar
  • 18 Einhorn L H, Donohue J P. Improved chemotherapy in disseminated testicular cancer.  J Urol. 1977;  117 65-69
    Suche in Google Scholar
  • 19 Einhorn L H, Brames M J, Juliar B. et al . Phase II study of paclitaxel plus gemcitabine salvage chemotherapy for germ cell tumors after progression following high-dose chemotherapy with tandem transplant.  J Clin Oncol. 2007;  25 513-516
    Suche in Google Scholar
  • 20 Faivre S, Raymond E, Woynarowski J M. et al . Supraadditive effect of 2’,2’-difluorodeoxycytidine (gemcitabine) in combination with oxaliplatin in human cancer cell lines.  Cancer Chemother Pharmacol. 1999;  44 117-123
    Suche in Google Scholar
  • 21 Germa-Lluch J R, Garcia del Muro X, Maroto P. et al . Clinical pattern and therapeutic results achieved in 1490 patients with germ-cell tumours of the testis: the experience of the Spanish Germ-Cell Cancer Group (GG).  Eur Urol. 2002;  42 553-562; discussion 562 – 553
    Suche in Google Scholar
  • 22 Glasgow S C, Yu J, Carvalho L P. et al . Unfavourable expression of pharmacologic markers in mucinous colorectal cancer.  Br J Cancer. 2005;  92 259-264
    Suche in Google Scholar
  • 23 Gordon M A, Gil J, Lu B. et al . Genomic profiling associated with recurrence in patients with rectal cancer treated with chemoradiation.  Pharmacogenomics. 2006;  7 67-88
    Suche in Google Scholar
  • 24 Hettinga J V, Lemstra W, Meijer C. et al . Heat-shock protein expression in cisplatin-sensitive and -resistant human tumor cells.  Int J Cancer. 1996;  67 800-807
    Suche in Google Scholar
  • 25 Hinton S CP, Einhorn L. et al . Phase II trial of paclitaxel and gemcitabine in refractory germ cell tumors.  J Clin Oncol. 2001;  20 1859-1863
    Suche in Google Scholar
  • 26 Huyghe E, Matsuda T, Thonneau P. Increasing incidence of testicular cancer worldwide: a review.  J Urol. 2003;  170 5-11
    Suche in Google Scholar
  • 27 Ishida S, Lee J, Thiele D J. et al . Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctr1 in yeast and mammals.  Proc Natl Acad Sci. USA 2002;  99 14 298-14 302
    Suche in Google Scholar
  • 28 Jordan K, Kegel T, Mueller L P. et al . Feasibility of a combination of high dose chemotherapy ifosfamide, carboplatin, etoposide (ICE) plus stem cells and bevacizumab in refractory sarcoma and germ cell tumors.  JCO. 2005;  23 9070
    Suche in Google Scholar
  • 29 Kersemaekers A M, Mayer F, Molier M. et al . Role of P53 and MDM2 in treatment response of human germ cell tumors.  J Clin Oncol. 2002;  20 1551-1561
    Suche in Google Scholar
  • 30 Koberle B, Masters J R, Hartley J A. et al . Defective repair of cisplatin-induced DNA damage caused by reduced XPA protein in testicular germ cell tumours.  Curr Biol. 1999;  9 273-276
    Suche in Google Scholar
  • 31 Kollmannsberger C, Nichols C, Bokemeyer C. Recent advances in management of patients with platinum-refractory testicular germ cell tumors.  Cancer. 2006;  106 1217-1226
    Suche in Google Scholar
  • 32 Kollmannsberger C, Beyer J, Liersch R. et al . Combination chemotherapy with gemcitabine plus oxaliplatin in patients with intensively pretreated or refractory germ cell cancer: a study of the German Testicular Cancer Study Group.  J Clin Oncol. 2004;  22 108-114
    Suche in Google Scholar
  • 33 Kollmannsberger C, Rick O, Derigs H G. et al . Activity of oxaliplatin in patients with relapsed or cisplatin-refractory germ cell cancer: a study of the German Testicular Cancer Study Group.  J Clin Oncol. 2002;  20 2031-2037
    Suche in Google Scholar
  • 34 Lowe S W, Ruley H E, Jacks T. et al . p53-dependent apoptosis modulates the cytotoxicity of anticancer agents.  Cell. 1993;  74 957-967
    Suche in Google Scholar
  • 35 Lowe S W, Schmitt E M, Smith S W. et al . p53 is required for radiation-induced apoptosis in mouse thymocytes.  Nature. 1993;  362 847-849
    Suche in Google Scholar
  • 36 Lutzker S G, Levine A J. A functionally inactive p53 protein in teratocarcinoma cells is activated by either DNA damage or cellular differentiation.  Nat Med. 1996;  2 804-810
    Suche in Google Scholar
  • 37 Lutzker S G, Mathew R, Taller D R. A p53 dose-response relationship for sensitivity to DNA damage in isogenic teratocarcinoma cells.  Oncogene. 2001;  20 2982-2986
    Suche in Google Scholar
  • 38 Masters J R, Koberle B. Curing metastatic cancer: lessons from testicular germ-cell tumours.  Nat Rev Cancer. 2003;  3 517-525
    Suche in Google Scholar
  • 39 Masters J R, Thomas R, Hall A G. et al . Sensitivity of testis tumour cells to chemotherapeutic drugs: role of detoxifying pathways.  Eur J Cancer. 1996;  32A 1248-1253
    Suche in Google Scholar
  • 40 Mayer F, Stoop H, Scheffer G L. et al . Molecular determinants of treatment response in human germ cell tumors.  Clin Cancer Res. 2003;  9 767-773
    Suche in Google Scholar
  • 41 Motzer R J, Mazumdar M, Sheinfeld J. et al . Sequential dose-intensive paclitaxel, ifosfamide, carboplatin, and etoposide salvage therapy for germ cell tumor patients.  J Clin Oncol. 2000;  18 1173-1180
    Suche in Google Scholar
  • 42 Mueller T, Voigt W, Simon H. et al . Failure of activation of caspase-9 induces a higher threshold for apoptosis and cisplatin resistance in testicular cancer.  Cancer Res. 2003;  63 513-521
    Suche in Google Scholar
  • 43 Nichols C R, Williams S D, Loehrer P J. et al . Randomized study of cisplatin dose intensity in poor-risk germ cell tumors: a Southeastern Cancer Study Group and Southwest Oncology Group protocol.  J Clin Oncol. 1991;  9 1163-1172
    Suche in Google Scholar
  • 44 Nuver J, Lutke Holzik M F, Zweeden M van. et al . Genetic variation in the bleomycin hydrolase gene and bleomycin-induced pulmonary toxicity in germ cell cancer patients.  Pharmacogenet Genomics. 2005;  15 399-405
    Suche in Google Scholar
  • 45 Oechsle K, Honecker F, Kollmannsberger C. et al . An open-label, multicenter phase II trial of capecitabine in patients with cisplatin-refractory or relapsed germ cell tumors.  Anticancer Drugs. 2007;  18 273-276
    Suche in Google Scholar
  • 46 Ohndorf U M, Whitehead J P, Raju N L. et al . Binding of tsHMG, a mouse testis-specific HMG-domain protein, to cisplatin-DNA adducts.  Biochemistry. 1997;  36 14 807-14 815
    Suche in Google Scholar
  • 47 Oliver R T, Mason M D, Mead G M. et al . Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial.  Lancet. 2005;  366 293-300
    Suche in Google Scholar
  • 48 Oosterhuis J W, Andrews P W, Knowles B B. et al . Effects of cis-platinum on embryonal carcinoma cell lines in vitro.  Int J Cancer. 1984;  34 133-139
    Suche in Google Scholar
  • 49 Park D J, Zhang W, Stoehlmacher J. et al . ERCC1 gene polymorphism as a predictor for clinical outcome in advanced colorectal cancer patients treated with platinum-based chemotherapy.  Clin Adv Hematol Oncol. 2003;  1 162-166
    Suche in Google Scholar
  • 50 Parris C N, Walker M C, Masters J R. et al . Inherent sensitivity and induced resistance to chemotherapeutic drugs and irradiation in human cancer cell lines: relationship to mutation frequencies.  Cancer Res. 1990;  50 7513-7518
    Suche in Google Scholar
  • 51 Parris C N, Arlett C F, Lehmann A R. et al . Differential sensitivities to gamma radiation of human bladder and testicular tumour cell lines.  Int J Radiat Biol Relat Stud Phys Chem Med. 1988;  53 599-608
    Suche in Google Scholar
  • 52 Pectasides D, Pectasides M, Farmakis D. et al . Gemcitabine and oxaliplatin (GEMOX) in patients with cisplatin-refractory germ cell tumors: a phase II study.  Ann Oncol. 2004;  15 493-497
    Suche in Google Scholar
  • 53 Pectasides D, Pectasides M, Farmakis D. et al . Oxaliplatin and irinotecan plus granulocyte-colony stimulating factor as third-line treatment in relapsed or cisplatin-refractory germ-cell tumor patients: a phase II study.  Eur Urol. 2004;  46 216-221
    Suche in Google Scholar
  • 54 Pera M F, Friedlos F, Mills J. et al . Inherent sensitivity of cultured human embryonal carcinoma cells to adducts of cis-diamminedichloroplatinum(II) on DNA.  Cancer Res. 1987;  47 6810-6813
    Suche in Google Scholar
  • 55 Richards E H, Hickman J A, Masters J R. Heat shock protein expression in testis and bladder cancer cell lines exhibiting differential sensitivity to heat.  Br J Cancer. 1995;  72 620-626
    Suche in Google Scholar
  • 56 Richards E H, Hickey E, Weber L. et al . Effect of overexpression of the small heat shock protein HSP27 on the heat and drug sensitivities of human testis tumor cells.  Cancer Res. 1996;  56 2446-2451
    Suche in Google Scholar
  • 57 Rick O, Braun T, Siegert W. et al . Activity of thalidomide in patients with platinum-refractory germ-cell tumours.  Eur J Cancer. 2006;  42 1775-1779
    Suche in Google Scholar
  • 58 Rick O, Bokemeyer C, Beyer J. et al . Salvage treatment with paclitaxel, ifosfamide, and cisplatin plus high-dose carboplatin, etoposide, and thiotepa followed by autologous stem-cell rescue in patients with relapsed or refractory germ cell cancer.  J Clin Oncol. 2001;  19 81-88
    Suche in Google Scholar
  • 59 Sark M W, Timmer-Bosscha H, Meijer C. et al . Cellular basis for differential sensitivity to cisplatin in human germ cell tumour and colon carcinoma cell lines.  Br J Cancer. 1995;  71 684-690
    Suche in Google Scholar
  • 60 Schmoll H J, Souchon R, Krege S. et al . European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG).  Ann Oncol. 2004;  15 1377-1399
    Suche in Google Scholar
  • 61 Seve P, Dumontet C. Chemoresistance in non-small cell lung cancer.  Current medicinal chemistry. 2005;  5 73-88
    Suche in Google Scholar
  • 62 Simon G R, Sharma S, Cantor A. et al . ERCC1 expression is a predictor of survival in resected patients with non-small cell lung cancer.  Chest. 2005;  127 978-983
    Suche in Google Scholar
  • 63 Souchon R, Krege S, Schmoll H J. et al . Interdisciplinary consensus on diagnosis and therapy of testicular tumors. Results of an update conference based on evidence-based medicine. German Testicular Cancer study Group (GTCSG).  Strahlenther Onkol. 2000;  176 388-405
    Suche in Google Scholar
  • 64 Theodore C FA, Fizazi K. et al . A phase II multicentre study of oxaliplatin (Ox) in combination with paclitaxel (Px) in patients (pts) who failed cisplatin (CDDP) based chemotherapy (CT) for germ cell tumors (GCT).  Proc Am Soc Clin Oncol. 2004;  23 389 (Abstr. 4534)
    Suche in Google Scholar
  • 65 Trimmer E E, Zamble D B, Lippard S J. et al . Human testis-determining factor SRY binds to the major DNA adduct of cisplatin and a putative target sequence with comparable affinities.  Biochemistry. 1998;  37 352-362
    Suche in Google Scholar
  • 66 Voigt W, Kegel T, Maher G. et al . Bevacizumab plus high-dose ifosfamide, etoposide and carboplatin (HD-ICE) as third-line salvage chemotherapy induced an unexpected dramatic response in highly platinum refractory germ-cell cancer.  Ann Oncol. 2006;  17 531-533
    Suche in Google Scholar
  • 67 Zafarana G, Gillis A J, Gurp R J van. et al . Coamplification of DAD-R, SOX5, and EKI1 in human testicular seminomas, with specific overexpression of DAD-R, correlates with reduced levels of apoptosis and earlier clinical manifestation.  Cancer Res. 2002;  62 1822-1831
    Suche in Google Scholar
  • 68 Zamble D B, Mikata Y, Eng C H. et al . Testis-specific HMG-domain protein alters the responses of cells to cisplatin.  J Inorg Biochem. 2002;  91 451-462
    Suche in Google Scholar

Dr. med. Jan Ebbing

Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin

Hindenburgdamm 30

12200 Berlin

Telefon: 030/8445–2577

Fax: 030/8445–4448

eMail: jan.ebbing@charite.de

    Editorial Comment zur Übersicht.