Limited access trial using amifostine for protection against cisplatin- and three-hour paclitaxel-induced neurotoxicity: a phase II study of the Gynecologic Oncology Group.
OBJECTIVE
The purpose of this study was to determine whether amifostine (WR-2721) prevents or ameliorates clinically significant (grade 2 to 4) neurotoxicity associated with cisplatin and 3-hour paclitaxel chemotherapy.


METHODS
The chemotherapy program consisted of intravenous paclitaxel 175 mg/m2 over 3 hours followed by amifostine 740 mg/m2 and cisplatin 75 mg/m2 administered over 90 minutes beginning 15 minutes after amifostine administration. At baseline, before each treatment cycle, and for 3 months after completing chemotherapy, patients were evaluated for evidence of neurotoxicity and other treatment-related adverse effects using three methods: standard clinical evaluation (National Cancer Institute common toxicity criteria [CTC] grading), a neurotoxicity questionnaire to assess symptoms and limitations imposed by peripheral neuropathy, and vibration perception threshold (VPT) testing.


RESULTS
Four of 27 assessable patients developed grade 2 to 4 neurotoxicity based on clinical assessments and CTC grading. This number of neuropathic events exceeded the predetermined threshold level for a second stage of accrual and the study was closed.


CONCLUSIONS
Amifostine's level of activity in this trial was insufficient to warrant further study in a phase III trial. Based on the receiver operating characteristic analysis, it would appear that VPT measurements are less sensitive to the development of peripheral neuropathy than the neurotoxicity questionnaire. The questionnaire, referred to as the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, may be used instead of VPT measurements in future studies of chemotherapy-induced peripheral neuropathy.
Moore
David H
DH
Department of Obstetrics/Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA.
Donnelly
James
J
McGuire
William P
WP
Almadrones
Lois
L
Cella
David F
DF
Herzog
Thomas J
TJ
Waggoner
Steven E
SE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004999:Amifostine / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009460:Neurologic Examination; D017239:Paclitaxel / Q000008:administration & dosage; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D011837:Radiation-Protective Agents; D004999:Amifostine; D017239:Paclitaxel; D002945:Cisplatin