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Limited Access Trial Using Amifostine for Protection Against Cisplatin- and Three-Hour Paclitaxel–Induced Neurotoxicity: A Phase II Study of the Gynecologic Oncology Group

David H. Moore, James Donnelly, William P. McGuire, Lois Almadrones, David F. Cella, Thomas J. Herzog, Steven E. Waggoner

From the Department of Obstetrics/Gynecology, Indiana University School of Medicine, Indianapolis, IN; Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo; Department of Gynecologic Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY; Cancer Center, Franklin Square Hospital, Baltimore, MD; Institute for Health Services Research and Policy Studies, Northwestern University, Evanston; Division of Obstetrics and Gynecology, University of Chicago, Chicago, IL; and Division of Gynecologic Oncology, Department of Obstetrics/Gynecology, Washington University School of Medicine, St Louis, MO.

Address reprint requests to Denise Mackey, Gynecologic Oncology Group, Four Penn Center, 1600 JFK Blvd, Suite 1020, Philadelphia, PA 19103.

Purpose: 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.

Materials and 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.

Conclusion: 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.

Supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (grant no. CA 27469), Philadelphia, PA, and the Gynecologic Oncology Group Statistical Office (grant no. CA 37517), Buffalo, NY.

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