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.
OBJECTIVE
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.


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).


CONCLUSIONS
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.
Hilpert
F
F
Klinik für Gynäkologie und Geburtshilfe, Campus Kiel Universitätsklinikum Schleswig-Holstein, Michaelisstrasse 16, 24105 Kiel, Germany. fhilpert@email.uni-kiel.de
Stähle
A
A
Tomé
O
O
Burges
A
A
Rossner
D
D
Späthe
K
K
Heilmann
V
V
Richter
B
B
du Bois
A
A
D000328:Adult; D004999:Amifostine / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005858:Germany; D006801:Humans; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D010919:Placebos; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D018696:Neuroprotective Agents; D010919:Placebos; D011837:Radiation-Protective Agents; D016190:Carboplatin; D004999:Amifostine; D017239:Paclitaxel