Obtain longitudinal pilot data including patient- and clinician-derived metrics, electrophysiology and tissue oxygen as potential biomarkers for chemotherapy induced peripheral neuropathy. Establish the relationship between tissue oxygen and existing biomarkers of CIPN.

CIPN is a common, dose-limiting effect of chemotherapeutic agents. A major shortfall in management of CIPN is absence of early predictors for those at greatest risk and sensitive, early biomarkers to identify onset.

Six breast cancer patients were studied prior to paclitaxel chemotherapy, mid-therapy and post-therapy. NCI-CTCAEv3, Total Neuropathy Score, Toronto Neuropathy Score, pain, quality of life, autonomic and electrophysiologic metrics were obtained at each point. A novel biomarker of tissue oxygen, electron paramagnetic resonance (EPR) oximetry, was correlated with electrophysiologic and clinical markers.

The average onset of symptoms was 31.5+2.1 days. No change in UE/LE function, well-being or social function was detected. Clinician rated scales showed an increase in neuropathy indices for all patients regardless of reported symptoms although NCI-CTCAEv3 was insensitive. All patients demonstrated loss of peroneal CMAP amplitude by visit 2 (21-34 days) regardless of symptoms. Reduced distal SNAP amplitude were seen in 2/3 patients by 21 days. Three patients showed increase in pain scores early on (mid-chemotherapy visit) but only one of those patients had a persistently elevated score at the post chemotherapy visit.

Using EPR oximetry data, all patients except one demonstrated a shift in tissue responsiveness from being nonreactive to conditions of hyperoxygenation to being reactive to hyperoxygenation after exposure to paclitaxel. One patient did not demonstrate this shift but was reactive to hyperoxygenation at baseline. This patient also reported higher pain ratings than other patients, particularly at the end of treatment.

EPR oximetry may be a biomarker of CIPN but additional data is needed to assess its utility. Clinician rated and electrophysiologic metrics were sensitive with the exception of NCI-CTCAEv3.