Novel neurosensory testing in cancer patients treated with the epothilone B analog, ixabepilone.
BACKGROUND
We have previously established the recommended phase II dose (RPTD) of ixabepilone as 40 mg/m(2) 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.


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.


CONCLUSIONS
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.
Goel
S
S
Department of Oncology, Albert Einstein College of Medicine and Cancer Center, Bronx, NY, USA. sgoel@montefiore.org
Goldberg
G L
GL
Kuo
D Y-S
DY
Muggia
F
F
Arezzo
J
J
Mani
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D034261:Epothilones / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009431:Neural Conduction / Q000187:drug effects; D009460:Neurologic Examination / Q000379:methods; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D020886:Somatosensory Disorders / Q000139:chemically induced*; D014732:Vibration
D000970:Antineoplastic Agents; D034261:Epothilones; C430592:ixabepilone