Aktuelle Urol 2024; 55(06): 543-548
DOI: 10.1055/a-2364-4213
Übersicht

Konventionell dosierte oder Hochdosis-Salvagetherapie bei rezidivierten Hodentumoren

Conventional versus high-dose salvage chemotherapy for relapsed testicular germ cell tumours
1   Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN5994)
2   Northern Centre for Cancer Care, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN5983)
3   II. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland (Ringgold ID: RIN37734)
,
Marcus Hentrich
4   Abteilung für Innere Medizin III, Rotkreuzklinikum München, München, Germany (Ringgold ID: RIN219606)
› Author Affiliations

Zusammenfassung

Patienten mit metastasierter Keimzelltumorerkrankung haben seit Einführung Cisplatin-basierter Kombinationschemotherapieregime sehr gute Heilungsaussichten von >80%. Trotzdem erleiden knapp 30% der Patienten nach der Erstlinientherapie ein Rezidiv ihrer Erkrankung. Knapp die Hälfte dieser Patienten kann durch platin-basierte Salvagechemotherapie und ggf. anschließende Residualtumorresektion geheilt werden. Für die Salvagechemotherapie kommen entweder erneut konventionell dosierte Cisplatin-basierte Kombinationstherapien oder eine Hochdosischemotherapie mit Carboplatin und Etoposid und nachfolgender autologer Stammzelltransplantation zum Einsatz. Bislang gibt es keine höhergradige Evidenz aus randomisierten Studien, die einen Vorteil für die Hochdosischemotherapie zeigen konnte, jedoch beschreibt eine internationale retrospektive Registerstudie mit knapp 1600 Patienten ein ca. 15% höheres Gesamtüberleben für Patienten, die dosisintensiviert behandelt wurden. Im vorliegenden Übersichtsartikel wird die Datenlage zu den unterschiedlichen Salvagetherapiestrategien zusammengefasst und unter Einbezug aktueller Leitlinienempfehlungen diskutiert.

Abstract

Since the introduction of cisplatin-based combination chemotherapy, patients with metastatic germ cell tumours achieve very high cure rates of >80%. Nevertheless, about 30% of patients relapse despite guideline-endorsed first-line treatment. Of these, again about 50% of patients can still achieve cure with platinum-based salvage chemotherapy and eventually post-chemotherapy residual mass resection.

Salvage chemotherapy generally involves platinum-based combination chemotherapy, either as conventional dose cisplatin-based combinations again or as high-dose chemotherapy with subsequent autologous stem cell transplantation.

To date, high level evidence from randomised trials supporting the use of salvage high-dose chemotherapy for all patients relapsing after first-line treatment remains lacking, but a large international retrospective registry study had shown a 15% overall survival benefit for patients undergoing salvage high-dose chemotherapy.

In this article, we summarise the available literature on the different salvage treatment approaches and discuss these in the light of current treatment guideline recommendations for the management of testicular cancer.



Publication History

Received: 21 May 2024

Accepted after revision: 08 July 2024

Article published online:
06 August 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 
  • Literatur

  • 1 Ko JJ, Bernard B, Tran B. et al. Conditional survival of patients with metastatic testicular germ cell tumors treated with first-line curative therapy. Journal of Clinical Oncology 2016; 34: 714-720
  • 2 Mead GM. 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
  • 3 Beyer J, Collette L, Sauvé N. et al. Survival and New Prognosticators in Metastatic Seminoma: Results From the IGCCCG-Update Consortium. J Clin Oncol 2021; 39: 1553-1562
  • 4 Gillessen S, Sauvé N, Collette L. et al. Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium. J Clin Oncol 2021; 39: 1563-1574
  • 5 Lorch A, Beyer J, Kramar A. et al. Prognostic factors in patients with metastatic germ cell tumors who experienced treatment failure with cisplatin-based first-line chemotherapy. J Clin Oncol 2010; 28: 4906-4911
  • 6 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft DK, AWMF) S3-Leitlinie Diagnostik, Therapie und Nachsorge der Keimzelltumoren des Hodens. In: Langversion 1.1. 2020 https://www.leitlinienprogramm-onkologie.de/fileadmin/user_upload/Downloads/Leitlinien/Hodentumoren/LL_Hodentumoren_Langversion_1.1.pdf
  • 7 Oldenburg J, Berney DM, Bokemeyer C. et al. Testicular seminoma and non-seminoma: ESMO-EURACAN Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2022; 33: 362-375
  • 8 Patrikidou A, Cazzaniga W, Berney D. et al. European Association of Urology Guidelines on Testicular Cancer: 2023 Update. Eur Urol 2023; 84: 289-301
  • 9 Pfister D, Oechsle K, Schmidt S. et al. First-line salvage treatment options for germ cell tumor patients failing stage-adapted primary treatment: A comprehensive review compiled by the German Testicular Cancer Study Group. World J Urol 2022; 40: 2853-2861
  • 10 Kondagunta GV, Bacik J, Donadio A. et al. Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors. J Clin Oncol 2005; 23: 6549-6555
  • 11 Motzer RJ, Cooper K, Geller NL. et al. The Role of Ifosfamide Plus Cisplatin-Based Chemotherapy as Salvage Therapy for Patients With Refractory Germ Cell Tumors. Cancer 1990; 66: 2476-2481
  • 12 Horstrick A, Schmoll HJ, Wilke H. et al. Cisplatin, etoposide, and ifosfamide salvage therapy for refractory or relapsing germ cell carcinoma. J Clin Oncol 1991; 9: 1549-1555
  • 13 Loehrer PJ, Gonin R, Nichols CR. et al. Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor. J Clin Oncol 1998; 16: 2500-2504
  • 14 Feldman DR, Sheinfeld J, Bajorin DF. et al. TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis. J Clin Oncol 2010; 28: 1706-1713
  • 15 Lorch A, Bascoul-Mollevi C, Kramar A. et al. Conventional-dose versus high-dose chemotherapy as first salvage treatment in male patients with metastatic germ cell tumors: evidence from a large international database. J Clin Oncol 2011; 29: 2178-2184
  • 16 Broun ER, Nichols CR, Tricot G. et al. High dose carboplatin/VP-16 plus ifosfamide with autologous bone marrow support in the treatment of refractory germ cell tumors. Bone Marrow Transplant 1991; 7: 53-56
  • 17 Motzer RJ, Mazumdar M, Bosl GJ. et al. High-dose carboplatin, etoposide, and cyclophosphamide for patients with refractory germ cell tumors: treatment results and prognostic factors for survival and toxicity. J Clin Oncol 1996; 14: 1098-1105
  • 18 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
  • 19 Margolin KA, Doroshow JH, Frankel P. et al. Paclitaxel-based high-dose chemotherapy with autologous stem cell rescue for relapsed germ cell cancer. Biol Blood Marrow Transplant 2005; 11: 903-911
  • 20 Selle F, Wittnebel S, Biron P. et al. A phase II trial of high-dose chemotherapy (HDCT) supported by hematopoietic stem-cell transplantation (HSCT) in germ-cell tumors (GCTs) patients failing cisplatin-based chemotherapy: the Multicentric TAXIF II study. Ann Oncol 2014; 25: 1775-1782
  • 21 Oing C, Lorch A. The Role of Salvage High-Dose Chemotherapy in Relapsed Male Germ Cell Tumors. Oncol Res Treat 2018; 41: 365-369
  • 22 Seidel C, Schaefers C, Connolly EA. et al. Efficacy and safety of high-dose chemotherapy as the first or subsequent salvage treatment line in patients with relapsed or refractory germ cell cancer: an international multicentric analysis. ESMO Open 2024; 9: 103449
  • 23 Adra N, Abonour R, Althouse SK. et al. High-Dose Chemotherapy and Autologous Peripheral-Blood Stem-Cell Transplantation for Relapsed Metastatic Germ Cell Tumors: The Indiana University Experience. J Clin Oncol 2017; 35: 1096-1102
  • 24 Lorch A, Kollmannsberger C, Hartmann JT. et al. Single versus sequential high-dose chemotherapy in patients with relapsed or refractory germ cell tumors: a prospective randomized multicenter trial of the German Testicular Cancer Study Group. J Clin Oncol 2007; 25: 2778-2784
  • 25 Lorch A, Kleinhans A, Kramar A. et al. Sequential versus single high-dose chemotherapy in patients with relapsed or refractory germ cell tumors: long-term results of a prospective randomized trial. J Clin Oncol 2012; 30: 800-805
  • 26 Einhorn LH, Williams SD, Chamness A. et al. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med 2007; 357: 340-348
  • 27 Collette L, Sylvester RJ, Stenning SP. et al. Impact of the treating institution on survival of patients with "poor-prognosis" metastatic nonseminoma. European Organization for Research and Treatment of Cancer Genito-Urinary Tract Cancer Collaborative Group and the Medical Research Council Testicular Cancer Working Party. J Natl Cancer Inst 1999; 91: 839-846
  • 28 McKiernan JM, Motzer RJ, Bajorin DF. et al. Reoperative retroperitoneal surgery for nonseminomatous germ cell tumor: Clinical presentation, patterns of recurrence, and outcome. Urology 2003; 62: 732-736
  • 29 Rick O, Bokemeyer C, Weinknecht S. et al. Residual tumor resection after high-dose chemotherapy in patients with relapsed or refractory germ cell cancer. J Clin Oncol 2004; 22: 3713-3719
  • 30 Heidenreich A, Ohlmann C, Hegele A. et al. Repeat retroperitoneal lymphadenectomy in advanced testicular cancer. Eur Urol 2005; 47: 64-71
  • 31 Oing C, Giannatempo P, Honecker F. et al. Palliative treatment of germ cell cancer. Cancer Treat Rev 2018; 71: 102-107
  • 32 Oing C, Alsdorf WH, Amsberg G von. et al. Platinum-refractory germ cell tumors: an update on current treatment options and developments. World J Urol 2017; 35: 1167-1175
  • 33 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
  • 34 Oechsle K, Kollmannsberger C, Honecker F. et al. Long-term survival after treatment with gemcitabine and oxaliplatin with and without paclitaxel plus secondary surgery in patients with cisplatin-refractory and/or multiply relapsed germ cell tumors. Eur Urol 2011; 60: 850-855
  • 35 Lorch A, Neubauer A, Hackenthal M. et al. High-dose chemotherapy (HDCT) as second-salvage treatment in patients with multiple relapsed or refractory germ-cell tumors. Ann Oncol 2010; 21: 820-825
  • 36 Oing C, Kollmannsberger C, Oechsle K. et al. Investigational targeted therapies for the treatment of testicular germ cell tumors. Expert Opin Investig Drugs 2016; 25: 1033-1043
  • 37 Mackensen A, Haanen JBAG, Koenecke C. et al. CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211–01 trial. Nat Med 2023; 29: 2844-2853