Annals of Hematology

, Volume 72, Issue 1, pp 1–9

Hematopoietic growth factors and treatment of testicular cancer: Biological interactions, routine use and dose-intensive chemotherapy

  • C. Bokemeyer
  • M. A. Kuczyk
  • H. Köhne
  • H. Einsele
  • B. Kynast
  • H. -J. Schmoll
Review Article

Abstract

With the use of aggressivecis-platinum-based combination chemotherapy the majority of patients with metastatic testicular cancer will be cured. Hematopoietic growth factors (HGFs), particularly G-and GM-CSF, have been investigated for the treatment of testicular cancer in order to (a) ameliorate chemotherapy-induced myelosuppression, (b) increase the dose intensity of treatment, or (c) generate peripheral blood stem cells (PBSC) as hematopoietic support for mega-dose chemotherapy. Results from in vitro and animal models have excluded a significant influence of both factors, G-CSF and GM-CSF, on tumor growth and response to cytotoxic treatment. For the group of ‘good-risk’ patients with metastatic testicular cancer, 85–90% of whom will reach long-term survival, the incidence of granulocytopenic infections after standard chemotherapy regimens appears to be lower than 20%. The prophylactic use of HGFs for these patients is not routinely recommended but may be considered in case of an increased risk for infections. For ‘risk’ patients, who will achieve a 50% survival following standard chemotherapy, different attempts of treatment intensification have been investigated. The use of aggressive multidrug regimens is associated with granulocytopenic infections in 20–70% of patients. A randomized trial has demonstrated that the prophylactic use of G-CSF significantly reduces granulocytopenia, the number of septic infections, and the infection-related death rate. For “poor-risk” patients the prophylactic use of HGFs, particularly G-CSF due to its favorable side effect profile, is recommended. The availability of G- and GM-CSF has made it possible to develop dose-intensified chemotherapy regimens. Demonstrated particularly for GM-CSF, a 1.5-fold dose increase can be achieved by the use of a myeloid growth factor alone, and thrombocytopenia and other organ toxicity will become dose limiting. Mobilization of PBSC, either after stimulation with HGFs alone or with HGFs, following chemotherapy has been successfully used in patients with testicular cancer. For the treatment of patients with relapsed disease PBSC support followed by HGFs has allowed the use of mega-dose therapy in multiple phase-II studies. This has prompted the investigation of high-dose therapy as first-line treatment for 'poor-risk' patients. In these patients sequential high-dose treatment withcis-platinum, etoposide, and ifosfamide for four consecutive cycles, each supported by G- or GM-CSF and PBSC, is currently being investigated by the German Testicular Cancer Study Group. HGFs have substantially reduced treatment-associated morbidity and mortality in patients receiving chemotherapy for testicular cancer. They make it possible for the first time to clinically explore the true value of dose-intensified chemotherapy regimens in testis cancer, serving as a model of a highly chemotherapy sensitive disease. Enrollment of patients in prospective clinical trials evaluating the role of high-dose therapy is strongly recommended.

Key words

Testicular cancer Germ cell tumors Hematopoietic growth factors G-CSF GM-CSF Stem cell factor (SCF) Peripheral blood stem cells (PBSC) Dose-intensive chemotherapy Neutropenia Infection Human testicular cancer cell lines 

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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • C. Bokemeyer
    • 1
  • M. A. Kuczyk
    • 2
  • H. Köhne
    • 4
  • H. Einsele
    • 1
  • B. Kynast
    • 3
  • H. -J. Schmoll
    • 3
  1. 1.Department of Internal Medicine IIUniversity of TübingenTübingenGermany
  2. 2.Department of UrologyHannover University Medical SchoolHannoverGermany
  3. 3.Department of Hematology/OncologyHannover University Medical SchoolHannoverGermany
  4. 4.Department of Hematology/OncologyRobert-Rössle-KlinikBerlinGermany

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