A promising biomarker strategy may help identify patients at risk for severe paclitaxel-induced neuropathy. Although weekly paclitaxel is more effective than a 3-weekly regimen, the treatment comes at the price of more severe sensory peripheral neuropathy (PN). As yet, treatment for chemotherapy-induced peripheral neuropathy (CIPN) is only symptomatic, say researchers from University of Singapore and National University Cancer Institute, Singapore.
Related: Is Chemotherapy a Good Choice for Neuroendocrine Tumors?
Their previous research, however, suggested that a protein called NDRG1 might be useful in predicting paclitaxel-induced PN. NDRG1 is a protein “ubiquitously” expressed in human tissues and tumors, the researchers note, particularly in peripheral nerve tissue. The protein also has been implicated in degrading myelin in Charcot-Marie-Tooth disease, a hereditary motor and sensory neuropathy.
Related: ASCO's Chemotherapy Administration Safety Standards
To expand on their earlier research, the researchers conducted another study in 111 patients with early stage breast cancer. Of those patients, 41% had human epidermal growth factor receptor (HER)-2 positive breast cancer and received adjuvant trastuzumab along with paclitaxel. Over a median of 12 weeks, 77 patients (69%) developed all-grade PN; in 17, the neuropathy was severe enough to mandate reducing or delaying doses or stopping paclitaxel. Peripheral neuropathy occurred before cycle 6 in 48%. Not surprisingly, patients with diabetes had more severe neuropathy (44% vs 11%). The researchers found no differences in neuropathy among various age groups or races; however, they also noted that most of the patients were Chinese.
Related: Palliative Chemotherapy May Be Harmful
The mean NDRG1 score of patients without severe neuropathy was 7.7, compared with 5.4 for patients with severe neuropathy. Fifty-four patients had an NDRGI score of < 7; of those, 13 (24%) developed severe neuropathy compared with only 4 of 57 (7%) of patients with a score above 7.
The researchers are performing a larger prospective study to explore the mechanisms of NDRG1 regulation to support their findings.
Source:
Sundar R, Jeyasekharan AD, Pang B, et al. PLoS ONE. 2016;11(10):e0164319.
doi:10.1371/journal.pone.0164319.
