Docetaxel-induced neuropathy:A pharmacogenetic case-control study of 150 women with early-stage breast cancer

<div><p></p><p><b>Background.</b> Docetaxel is a highly effective treatment of a wide range of malignancies but is often associated with peripheral neuropathy. The genetic variability of genes involved in the transportation or metabolism of docetaxel may be responsible for the variation in docetaxel-induced peripheral neuropathy (DIPN). The main purpose of this study was to investigate the impact of genetic variants in <i>GSTP1</i> and <i>ABCB1</i> on DIPN.</p><p><b>Material and methods.</b> DNA was extracted from whole blood from 150 patients with early-stage breast cancer who had received adjuvant docetaxel from February 2011 to May 2012. Two polymorphisms in <i>GSTP1</i> and three in <i>ABCB1</i> were selected for the primary analysis, and a host of other candidate genes was explored and compared between 75 patients with clinician-reported DIPN grade ≥ 2 and 75 patients without DIPN.</p><p><b>Results.</b> Patients with the genetic variants <i>GSTP1</i> rs1138272 C/T or T/T (114Ala/114Val or 114Val/114Val) genotype had an adjusted odds ratio of 3.82; 95% confidence interval 1.34–11.09 of developing DIPN. This result was confirmed in both analysis of cumulated docetaxel dose and haplotype analysis. None of the explorative genes investigated were significantly correlated with DIPN. Patients with a BMI ≥ 30 were five-fold more likely to have DIPN than patients with BMI < 25.</p><p><b>Conclusion.</b> We found that <i>GSTP1</i> Ala114Val polymorphism is associated with occurrence of DIPN. This supports the theory that oxidative stress is involved in DIPN pathophysiology. If confirmed, this may be helpful in the risk assessment of DIPN and perhaps help to achieve better management of neurotoxicity.</p></div

Addressing Chemotherapy-Induced Peripheral Neuropathy Using Multi-Frequency Vibrometry and Patient-Reported Outcomes

(1) The study evaluated correlations between multi-frequency vibrometry (MF-V) and the measure of chemotherapy-induced peripheral neuropathy developed by the European Organization for the Research and Treatment of Cancer (CIPN18). (2) Patients with cancer scheduled to undergo treatment with capecitabine and oxaliplatin (CAPOX) or carboplatin and paclitaxel (Carbo-Tax) were recruited in a prospective, observational study with MF-V and the CIPN18 from baseline to one year after end of treatment. (3) The study recruited 31 evaluable patients. All MF-V measurements correlated significantly with the CIPN18 scores (r = 0.25&ndash;0.48, p &gt; 0.003), with a low frequency (32 Hz) from metatarsals showing the best correlation coefficients (0.059 Z-score per CIPN18 point change, r = 0.48, CI-95 = [0.32; 0.60], p &gt; 0.0001). The largest change in MF-V scores from baseline was seen in low-frequency VPTs taken from metatarsals at 8 Hz three months after end of treatment (from &minus;0.26, CI-95 [&minus;0.85, 0.38] to 1.15, CI-95 [0.53, 1.84]) for patients treated with oxaliplatin and at 32 Hz one year after end of treatment (from 0.09, CI-95 [&minus;0.56, 0.77] to 0.88, CI-95 [0.34, 1.47]) for patients treated with paclitaxel. (4) Low-frequency vibration perception thresholds (8 and 32 Hz) correlated better with CIPN18 scores than high-frequency ones (128 and 250 Hz). If validated, this finding will advance CIPN pathophysiological understanding and inform the development of assessment methods