Supportive Care in Cancer

, Volume 13, Issue 10, pp 797–805 | Cite as

Neuroprotection with amifostine in the first-line treatment of advanced ovarian cancer with carboplatin/paclitaxel-based chemotherapy—a double-blind, placebo-controlled, randomized phase II study from the Arbeitsgemeinschaft Gynäkologische Onkologoie (AGO) Ovarian Cancer Study Group

  • F. Hilpert
  • A. Stähle
  • O. Tomé
  • A. Burges
  • D. Rossner
  • K. Späthe
  • V. Heilmann
  • B. Richter
  • A. du Bois
Original Article

Abstract

Goals of work

Neurotoxicity is a common side effect of platinum/taxane-based therapy of ovarian cancer. We performed a double-blind randomized placebo-controlled trial to evaluate the influence of the cytoprotectant amifostine on the neurotoxicity of first-line therapy of ovarian cancer with paclitaxel/carboplatin with or without epirubicin.

Patients and methods

Of 72 patients randomized, 71 were treated with paclitaxel 175 mg/m2 and carboplatin AUC5 with or without epirubicin 60 mg/m2 (q21×6) and randomized for i.v. premedication with amifostine 740 mg/m2 or placebo. Assessment included a questionnaire, NCI-CTC, tendon reflex activity (TRA), two-point discrimination (2-PD), measurement of vibration perception threshold (VPT) and vibration disappearance threshold (VDT), and quality of life.

Results

The majority of neurotoxicity criteria showed a significant impairment during therapy in both treatment arms. A significant protective effect of amifostine was observed for 2-PD, TRA, VPT and VDT. Amifostine failed to improve the ‘global health status quality of life’ score significantly. Toxicities according to NCI-CTC showed improved sensory neuropathy (P=0.0046) but a worsening in terms of nausea (P=0.0005) and vomiting (P=0.0083). No significant differences were observed for single sensory and motor symptoms, except for a better skilfulness in the amifostine group (P=0.0404).

Conclusion

Amifostine improved sensory neuropathy according to NCI-CTC and with regard to objective neurological assessment, but there were almost no differences in self-estimated specific sensory or motor symptoms. Disadvantages with regard to non-neurological toxicities and inconsistent results for quality of life demand further evaluation of neuroprotection with amifostine as well as alternative approaches to prevent platinum-taxane induced neurotoxicity.

Keywords

Ovarian cancer Neurotoxicity Amifostine Neuroprotection Vibration perception 

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • F. Hilpert
    • 1
  • A. Stähle
    • 2
  • O. Tomé
    • 3
  • A. Burges
    • 4
  • D. Rossner
    • 5
  • K. Späthe
    • 6
  • V. Heilmann
    • 7
  • B. Richter
    • 8
    • 9
  • A. du Bois
    • 2
    • 10
  1. 1.Klinik für Gynäkologie und GeburtshilfeCampus Kiel Universitätsklinikum Schleswig-HolsteinKielGermany
  2. 2.FrauenklinikSt. Vincentius-Krankenhäuser KarlsruheKarlsruheGermany
  3. 3.UniversitätsfrauenklinikUniversitätsklinikum TübingenTübingenGermany
  4. 4.Zentrum für FrauenheilkundeKlinikum Großhadern MünchenMünchenGermany
  5. 5.FrauenklinikMedizinische Hochschule HannoverHannoverGermany
  6. 6.Frauen- und PoliklinikKlinikum rechts der Isar der Technischen Universität MünchenMünchenGermany
  7. 7.UniversitätsfrauenklinikUniversitätsklinikum UlmUlmGermany
  8. 8.Klinik und Poliklinik für FrauenheilkundeCarl-Gustav-Carus Universität DresdenDresdenGermany
  9. 9.FrauenklinikElblandkliniken Meißen-Radebeul Standort RadebeulRadebeulGermany
  10. 10.Department for Gynecology and Gynecologic OncologyDr.-Horst-Schmidt-Kliniken GmbH, WiesbadenWiesbadenGermany

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