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Annals of Oncology Advance Access originally published online on July 21, 2008
Annals of Oncology 2008 19(12):2048-2052; doi:10.1093/annonc/mdn420
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

quality of life

Novel neurosensory testing in cancer patients treated with the epothilone B analog, ixabepilone

S. Goel1,2,*, G. L. Goldberg1,3, D. Y.-S. Kuo1,3, F. Muggia4, J. Arezzo5 and S. Mani1,2

1 Department of Oncology, Albert Einstein College of Medicine and Cancer Center, Bronx
2 Department of Oncology, Montefiore Medical Center, Bronx
3 Division of Gynecologic Oncology, Montefiore Medical Center, Bronx
4 Department of Oncology, NYU Center Institute, New York University, New York
5 Department of Neuroscience, Albert Einstein College of Medicine, Bronx, USA

* Correspondence to: Sanjay Goel, Asst Prof of Medicine, Department of Oncology, Montefiore Medical Center, 1825 Eastchester Road, Bronx, NY 10461, USA. Tel: +1-718-904-2488; Fax: +1-718-904-2830; E-mail: sgoel{at}montefiore.org

Background: We have previously established the recommended phase II dose (RPTD) of ixabepilone as 40 mg/m2 administered over 1 h repeated every 3 weeks with neuropathy as a cumulative dose-limiting toxicity. We expanded the cohort at the RPTD to include detailed assessment of nerve damage in these patients. We report our findings on vibration perception threshold (VPT) and neuropathy.

Patients and methods: Forty-four patients were treated with a median (range) of three (1–14) cycles of ixabepilone. The VPT (5-min duration) and nerve conduction test (NCT, 10-min duration) were carried out in the office, before ixabepilone dosing, and every two cycles thereafter.

Results: Neuropathy (grade 1 and grades 2–3) was observed in 17 (38.6%) and 11 (25%) patients, respectively. The mean increase in VPT as a function of grade 0–1 versus grades 2–3 neuropathy was 0.235 ± 0.03 versus 0.869 ± 0.09 (P = 0.049) vibration units. The F-wave frequency and distal motor latency, as assessed using the NCT, did not correlate with clinical neurotoxicity.

Conclusion: The change in VPT is observed early and likely reflects early vibration perception change. Mean change in VPT correlates with the severity of clinical neuropathy. Whether VPT change predicts onset of severe neuropathy warrants prospective testing and validation.

Key words: ixabepilone, nerve conduction test (NCT), phase I, solid tumors, vibration perception threshold (VPT)

Received for publication April 15, 2008. Revision received May 20, 2008. Accepted for publication June 9, 2008.


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