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 Gynakologische Onkologoie (AGO) Ovarian Cancer Study Group.

Author(s): Hilpert F, Stahle A, Tome O, Burges A, Rossner D, Spathe K, Heilmann V, Richter B, du Bois A, Arbeitsgemeinschaft Gynakologische Onkologoie (AGO) Ovarian Cancer Study Group

Affiliation(s): Klinik fur Gynakologie und Geburtshilfe, Campus Kiel Universitatsklinikum Schleswig-Holstein, Michaelisstrasse 16, 24105 Kiel, Germany. fhilpert@email.uni-kiel.de

Publication date & source: 2005-10, Support Care Cancer., 13(10):797-805. Epub 2005 Jul 16.

Publication type: Clinical Trial, Phase II; Randomized Controlled Trial

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 x 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.