early detection of taxane-induced neuropathy in women with breast cancer

Conditions: Peripheral Neuropathy

Summary: purpose: the purpose of the study is to test a new way of measuring nerve damage in women with breast cancer receiving chemotherapy drug paclitaxel (taxol).

purpose: the study has four aims; * the primary aim of the study is to determine whether women who are receiving either weekly taxol (80-100 mg/m2) or bi-weekly taxol (i.e.,dose-dense; 175 mg/m2) show deficits in axon-reflex mediated vasodilation (amv) over the course of six weeks of taxol therapy similar to those that have been reported in patients with diabetic and genetically-inherited neuropathies. * the second aim of the study is to determine whether women who are receiving either weekly or dose-dense taxol develop changes in amv before developing signs \& symptoms of chemotherapy-induced peripheral neuropathy (cipn) in a way that supports using changes in amv as an early detection method for small-fiber cipn. * a third (exploratory) aim of the study is to determine whether any changes in amv detected during the study are significantly correlated with self-reported cipn in a way that would support using changes in amv as a confirmatory marker for cipn. * a final (exploratory) aim of the study is to describe the size of axon reflexes and axon flares in women receiving weekly taxol before they start their pre-taxol anthracycline \& cyclophosphamide (ac) therapy.

Eligibility criteria:
inclusion criteria for women with breast cancer: * age 18-85 * able to read, write, and understand english * diagnosed with histologically-confirmed, first-time, non-metastatic breast cancer (stage i-iiib) * no prior exposure to neurotoxic chemotherapy or radiation at the time of enrollment, * will be receiving weekly paclitaxel (taxol® or generic paclitaxel, 80- 100mg/m2) or bi-weekly taxol (i.e., dose-dense; 175 mg/m2) as a part of their cancer treatment regimen or * will be receiving an anthracycline and cyclophosphamide (ac) followed by weekly paclitaxel (taxol® or generic paclitaxel, 80-100mg/m2) or bi-weekly taxol (i.e., dose-dense; 175 mg/m2) as a part of their cancer treatment regimen; inclusion criteria for healthy controls: * aged 18-85 * can read, write, and understand english exclusion criteria: * a history of cardiovascular disease, hypertension, or peripheral arterial/vascular disease; * current use of (1) medications/supplements to control blood pressure (e.g. beta-blockers, nitrates, calcium channel blockers, phosphodiesterase-5 (pge5) inhibitors) or (2) the use of statins for cholesterol; * suspected or diagnosed diabetes (with the exception of gestational diabetes); * pre-existing neuropathy, neuropathic pain, or nerve injury; * pain or significant arthritis in the toes of either foot; * current skin disease or fungal infection of the feet; * significant damage or deformity to the feet that would alter blood flow or make it impossible to measure/interpret findings; * diagnosed or suspected vasospastic disease such as raynaud's syndrome; * current use of tobacco/tobacco-containing products; * diagnosis of restless leg syndrome or other movement disorders that would prevent accurate data from being able to be collected. in-study restrictions: * no caffeine- or alcohol-containing products for 12 hours prior to their study visit; * no food for at least one hour prior to blood flow monitoring; * no non-steroidal anti-inflammatory drugs (nsaids) for 24 hours prior to study visits unless directed by a physician to do so. (note: these restrictions are designed to improve the rigor and quality of the data, but non-compliance will not be grounds for study exclusion; adherence to these restrictions will be monitored during self-report).

Keywords: taxane neuropathy chemotherapy-induced peripheral neuropathy (cipn) breast cancer local skin heating axon reflex axon flare total neuropathy score (tns) laser doppler flowmetry (ldf) laser speckle contrast imaging (lsci) full-field laser perfusion imaging (flpi) paclitaxel taxol