New diagnostic measures of oxaliplatin-induced peripheral sensory neuropathy

OBJECTIVE: Oxaliplatin-induced peripheral neuropathy (OIPN) is an unwanted side effect of oxaliplatin chemotherapy treatment. OIPN manifests in an acute phase that lasts a few days after injection and a persistent phase that may become chronic. Currently, there is no consensus about a clinically applicable, quantitative, and objective measure of OIPN.

METHODS: Seventeen patients treated with oxaliplatin containing adjuvant chemotherapy for stage III colon cancer, but otherwise healthy, were tested with six quantitative sensory tests (QST) and five large fibre perception threshold tracking (PTT) measures (quantified by, e.g., rheobase and electrotonus threshold) one hour before each of the 12 chemotherapy cycles given at two weeks' intervals. These measures were repeated at 3, 6, and 12-month follow-ups. The temporal development of OIPN assessed by the Common Terminology Criteria for Adverse Events (CTCAE) scale, QST, and PTT measures was calculated by linear regression.

RESULTS: The CTCAE score showed a tri-phasic increase during the treatment and remained increased during the follow-up. The vibration threshold (R = 0.25, p<0.001), the cold pain threshold (R = 0.17, p = 0.02), and the rheobase (R = 0.28, p < 0.001) increased during treatment, whereas the cold detection threshold (R=-0.16, p = 0.002) decreased. The cold pain threshold and the rheobase remained increased, and the cold detection and heat pain threshold remained decreased during follow-up.

CONCLUSIONS: Increased cold pain sensitivity and decreased large fibre sensitivity (increased rheobase) correlate to the persistent OIPN, whereas the CTCAE score assesses both acute and persistent OIPN. Furthermore, the novel PTT method assessed the nerve excitability changes caused by the oxaliplatin.