Oxaliplatin-associated neuropathy: a blood marker unrelated to symptoms in an exploratory study

Putting a marker of nerve damage to the test

The authors start with a gap: reliable circulating biomarkers of chemotherapy-induced peripheral neuropathy have yet to be established. They studied phosphorylated neurofilament heavy chain, or pNF-H, a marker of neuroaxonal injury whose clinical relevance during oxaliplatin treatment had not been demonstrated.

This multicenter prospective study included 30 patients with evaluable blood samples. All were being treated for unresectable or recurrent colorectal cancer with CapeOX plus bevacizumab. They were taking part in a randomized trial of a Japanese herbal preparation, but the analysis presented here focused on biomarker monitoring.

A biological increase that did not reflect neuropathy

Samples were collected before treatment, at the onset of clinically assessed neuropathy, and then at its resolution, at the ninth cycle or upon treatment discontinuation, whichever occurred first. Neuropathy was assessed using the CTCAE classification, version 5.0.

Plasma pNF-H concentrations varied widely between patients, with no uniform pattern over time. At the final sampling, they were modestly but significantly higher than at baseline and at neuropathy onset. However, the abstract does not provide the numerical magnitude of this difference.

Most importantly, concentrations were not associated with the onset, severity or persistence of clinically assessed neuropathy. A statistically significant change in the marker was therefore not enough to make it a clinically useful indicator.

A biological hypothesis, not a proven explanation

The researchers suggest a possible mismatch between what pNF-H measures, which relates to axonal damage, and damage to neuronal cell bodies in the dorsal root ganglia. This interpretation is a biological hypothesis, not a demonstration of the mechanism explaining the results.

This small study therefore does not validate pNF-H for monitoring neuropathy during oxaliplatin treatment. Nor does it allow conclusions about the effectiveness of the herbal preparation studied in the original trial: the abstract provided concerns the biomarker, not a therapeutic benefit.

What we can take away

Measuring pNF-H was technically possible, but its concentrations did not reflect clinical neuropathy in this study. The feasibility of an assay does not amount to validation of a monitoring tool.