This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gelmon, K. Articles by Iglesias, J. Search for Related Content PubMed PubMed Citation Articles by Gelmon, K. Articles by Iglesias, J. Social Bookmarking                            What's this?

Randomized Phase II Study of High-Dose Paclitaxel With or Without Amifostine in Patients With Metastatic Breast Cancer

From the British Columbia Cancer Agency, Vancouver; National Cancer Institute of Canada Clinical Trials Group, Kingston; Mount Sinai Hospital and Eli Lilly Company, Toronto; Ottawa Regional Cancer Centre, Ottawa; and McGill University, Montreal, Canada.

Address reprint requests to Karen A. Gelmon, MD, BCCA Vancouver Cancer Centre, 600 West 10th Ave, Vancouver, British Columbia, Canada V5Z 4E6; email kgelmon{at}bccancer.bc.ca

PURPOSE: To determine whether the neurotoxicity of paclitaxel 250 mg/m² given over 3 hours every 3 weeks could be reduced by pretreatment with amifostine 910 mg/m². Secondary objectives included comparing myelosuppression, myalgias, and response rates of the two groups.

PATIENTS AND METHODS: Forty womenwith metastatic breast cancer were randomized to receive either paclitaxel alone (arm 1) or paclitaxel preceded by amifostine (arm 2). All were assessable for toxicity, and 37 were assessable for response. At baseline and after each cycle, all patients completed questionnaires for neurologic symptoms and had standardized neurologic examinations, including objective assessments of power and vibration sense. In addition, standard follow-up assessments for other toxicities and tumor response were undertaken. Changes from baseline after courses 1, 2, and 3 were assessed. The sample size was sufficient to detect a 50% improvement in the expected determination in sensory change.

RESULTS: There were no differences observed in any of the measures of neurotoxicity. Other toxicity was similar in arms 1 and 2, including hair loss (95% v 90%), neurosensory changes (100% v 100%), fatigue/lethargy (85% v 90%), myalgia (95% v 90%), and grade 4 neutropenia (47% v 60%). Nausea, vomiting, dizziness, hypotension, and sneezing were more common in the amifostine arm. Response rates (22.2% v 36.8%) and paclitaxel pharmacokinetics were not significantly different.

CONCLUSION: There was no protection from paclitaxel-related neurotoxicity or hematologic toxicity in this study. These results suggest that the mechanism of action of paclitaxel-related toxic effects is not amenable to the cytoprotective action of amifostine.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J. J. Lee and S. M. Swain Peripheral Neuropathy Induced by Microtubule-Stabilizing Agents J. Clin. Oncol., April 1, 2006; 24(10): 1633 - 1642. [Abstract] [Full Text] [PDF]

				V. H. Nguyen and H. J. Lawrence Use of Gabapentin in the Prevention of Taxane-Induced Arthralgias and Myalgias J. Clin. Oncol., May 1, 2004; 22(9): 1767 - 1769. [Full Text] [PDF]

				H. Openshaw, K. Beamon, T. W. Synold, J. Longmate, N. E. Slatkin, J. H. Doroshow, S. Forman, K. Margolin, R. Morgan, S. Shibata, et al. Neurophysiological Study of Peripheral Neuropathy after High-Dose Paclitaxel: Lack of Neuroprotective Effect of Amifostine Clin. Cancer Res., January 15, 2004; 10(2): 461 - 467. [Abstract] [Full Text] [PDF]

				D. Lorusso, G. Ferrandina, S. Greggi, A. Gadducci, S. Pignata, S. Tateo, R. Biamonte, L. Manzione, G. Di Vagno, F. Ferrau', et al. Phase III multicenter randomized trial of amifostine as cytoprotectant in first-line chemotherapy in ovarian cancer patients Ann. Onc., July 1, 2003; 14(7): 1086 - 1093. [Abstract] [Full Text] [PDF]

				S. S. Leong, E. H. Tan, K. W. Fong, E. Wilder-Smith, Y. K. Ong, B. C. Tai, L. Chew, S. H. Lim, J. Wee, K. M. Lee, et al. Randomized Double-Blind Trial of Combined Modality Treatment With or Without Amifostine in Unresectable Stage III Non-Small-Cell Lung Cancer J. Clin. Oncol., May 1, 2003; 21(9): 1767 - 1774. [Abstract] [Full Text] [PDF]

				G. Freyer, P. Hennebert, A. Awada, T. Gil, J. Kerger, J. Selleslags, C. Brassinne, M. Piccart, and D. de Valeriola Influence of Amifostine on the Toxicity and Pharmacokinetics of Docetaxel in Metastatic Breast Cancer Patients: A Pilot Study Clin. Cancer Res., January 1, 2002; 8(1): 95 - 102. [Abstract] [Full Text] [PDF]

				L. Vahdat, K. Papadopoulos, D. Lange, S. Leuin, E. Kaufman, D. Donovan, D. Frederick, E. Bagiella, A. Tiersten, G. Nichols, et al. Reduction of Paclitaxel-induced Peripheral Neuropathy with Glutamine Clin. Cancer Res., May 1, 2001; 7(5): 1192 - 1197. [Abstract] [Full Text]

				J. F. Diaz, R. Strobe, Y. Engelborghs, A. A. Souto, and J. M. Andreu Molecular Recognition of Taxol by Microtubules. KINETICS AND THERMODYNAMICS OF BINDING OF FLUORESCENT TAXOL DERIVATIVES TO AN EXPOSED SITE J. Biol. Chem., August 18, 2000; 275(34): 26265 - 26276. [Abstract] [Full Text] [PDF]