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

Eckhoff, Lise; Feddersen, Søren; Knoop, Ann; Ewertz, Marianne; Bergmann, Troels K.

doi:10.3109/0284186x.2014.969846

Cited by 40 publications

(56 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with previous reports in patients with colon cancer who received oxaliplatin 96 and patients with breast cancer who received docetaxel, 97 as well as patients with fibromyalgia 98 and diabetes mellitus, 99 patients with CIN had a higher BMI. As expected, and consistent with recent studies, 78,100 patients with CIN were more likely to have received a combination of a platinum and a taxane compound and had received higher cumulative doses of CTX.…”

Section: Discussionsupporting

confidence: 90%

Chemotherapy-Induced Neuropathy in Cancer Survivors

Miaskowski

Mastick

Paul

et al. 2017

Journal of Pain and Symptom Management

100

View full text Add to dashboard Cite

Context Evidence suggests that chemotherapy-induced neuropathy (CIN) is a significant problem for cancer survivors. However, a detailed phenotypic characterization of CIN in cancer survivors is not available. Objectives To evaluate between group differences in demographic and clinical characteristics, as well as in measures of sensation, function, and postural control, in a sample of cancer survivors who received a platinum and/or a taxane-based CTX regimen and did (n=426) and did not (n=197) develop CIN. Methods Survivors completed self-report questionnaires and underwent objective testing (i.e., light touch, pain sensation, cold sensation, vibration, muscle strength, grip strength, Purdue Pegboard test, Timed Get Up and Go Test, Fullerton Advanced Balance test). Parametric and non-parametric statistics were used to compare between group differences in study outcomes. Results Of the 426 survivors with CIN, 4.9% had CIN only in their upper extremities, 27.0% only in their lower extremities, and 68.1% in both their upper and lower extremities. Demographic and clinical characteristics associated with CIN included: older age, lower annual income, higher body mass index, a higher level of comorbidity, being born prematurely, receipt of a higher cumulative dose of chemotherapy, and a poorer functional status. Survivors with CIN had worse outcomes for all of the following objective measures: light touch, pain, temperature, vibration, upper and lower extremity function and balance. Conclusions This study is the first to provide a detailed phenotypic characterization of CIN in cancer survivors who received a platinum and/or a taxane compound. These data can serve as a benchmark for future studies of CIN in cancer survivors.

show abstract

Section: Discussionsupporting

confidence: 90%

Chemotherapy-Induced Neuropathy in Cancer Survivors

Miaskowski

Mastick

Paul

et al. 2017

Journal of Pain and Symptom Management

100

View full text Add to dashboard Cite

show abstract

“…Alternatively, heterogeneity between the patient cohorts, including differences in gender, age, and functional status, or differences in the phenotype (grade 2+ vs. grade 3+), may explain the lack of replication across the clinical GWAS. This GWAS was also not able to replicate previously reported associations between docetaxel-induced neuropathy and SNPs in ABCB1 (15) or GSTP1 (13, 14) reported in previous candidate SNP studies, similar to the failure of paclitaxel GWAS to replicate associations with candidate SNPs including CYP2C8*3 (32). …”

Section: Discussioncontrasting

confidence: 77%

Pharmacogenetic Discovery in CALGB (Alliance) 90401 and Mechanistic Validation of a VAC14 Polymorphism that Increases Risk of Docetaxel-Induced Neuropathy

Hertz

Owzar

Lessans

et al. 2016

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose Discovery of single nucleotide polymorphisms (SNPs) that predict a patient's risk of docetaxel-induced neuropathy would enable treatment individualization to maximize efficacy and avoid unnecessary toxicity. The objectives of this analysis were to discover SNPs associated with docetaxel-induced neuropathy and mechanistically validate these associations in preclinical models of drug-induced neuropathy. Experimental Design A genome-wide association study was conducted in metastatic castrate-resistant prostate cancer patients treated with docetaxel, prednisone and randomized to bevacizumab or placebo on CALGB 90401. SNPs were genotyped on the Illumina HumanHap610-Quad platform followed by rigorous quality control. The inference was conducted on the cumulative dose at occurrence of grade 3+ sensory neuropathy using a cause-specific hazard model that accounted for early treatment discontinuation. Genes with SNPs significantly associated with neuropathy were knocked down in cellular and mouse models of drug-induced neuropathy. Results 498,081 SNPs were analyzed in 623 Caucasian patients, 50 (8%) of whom experienced grade 3+ neuropathy. The 1000 SNPs most associated with neuropathy clustered in relevant pathways including neuropathic pain and axonal guidance. A SNP in VAC14 (rs875858) surpassed genome-wide significance (p=2.12×10-8 adjusted p=5.88×10-7). siRNA knockdown of VAC14 in stem cell derived peripheral neuronal cells increased docetaxel sensitivity as measured by decreased neurite processes (p=0.0015) and branches (p<0.0001). Prior to docetaxel treatment VAC14 heterozygous mice had greater nociceptive sensitivity than wild-type litter mate controls (p=0.001). Conclusions VAC14 should be prioritized for further validation of its potential role as a predictor of docetaxel-induced neuropathy and biomarker for treatment individualization.

show abstract

“…[41][42][43] In that literature, marital satisfaction, spousal support, and spousal responses to pain reportedly can contribute to psychological distress (depressive symptoms, anxiety symptoms, and mood disorders) which, in turn, is associated with pain dimensions, including symptom severity. 4,11,39,40,44 In the current study, a history of vigorous exercise prior to chemotherapy was not identified as a factor in the development of CIPN, although other studies have shown significantly reduced CIPN in women who were physically active prior to receiving chemotherapy. In our multivariable model, these quality-of-life measures were collected before, not after, neurotoxic chemotherapy was received.…”

Section: Discussionmentioning

confidence: 49%

Patient‐reported and clinician‐reported chemotherapy‐induced peripheral neuropathy in patients with early breast cancer: Current clinical practice

Nyrop

Deal

Reeder-Hayes

et al. 2019

Cancer

View full text Add to dashboard Cite

BACKGROUND: In the current study, the authors investigated the incidence of moderate to severe chemotherapy-induced peripheral neuropathy (CIPN) for chemotherapy regimens commonly used in current clinical practice for the treatment of patients with early breast cancer. Patient-reported and clinician-assessed CIPN severity scores were compared, and risk factors for CIPN severity were identified. METHODS: Patients completed a Patient-Reported Symptom Monitoring form and oncologists completed a Common Terminology Criteria for Adverse Events form. CIPN reports were collected prospectively during regularly scheduled infusion visits throughout the duration of chemotherapy. RESULTS: The sample included 184 women with a mean age of 55 years; approximately 73% were white. The 4 chemotherapy regimens used were doxorubicin and cyclophosphamide plus paclitaxel (60 patients); docetaxel and cyclophosphamide (50 patients); docetaxel, carboplatin, and anti-human epidermal growth factor receptor 2 (HER2) (24 patients); and doxorubicin and cyclophosphamide plus paclitaxel and carboplatin (18 patients). All patients treated with doxorubicin and cyclophosphamide plus paclitaxel and doxorubicin and cyclophosphamide plus paclitaxel and carboplatin received paclitaxel; all patients treated with docetaxel and cyclophosphamide and docetaxel, carboplatin, and anti-HER2 received docetaxel. The chemotherapy dose was reduced in 52 patients (28%); in 15 patients (29%), this reduction was due to CIPN. Chemotherapy was discontinued in 26 patients (14%), 8 because of CIPN. Agreement between patient-reported and clinician-assessed CIPN severity scores was minimal (weighted Cohen kappa, P = .34). Patient-reported moderate to severe CIPN was higher for paclitaxel (50%) compared with docetaxel (17.7%) (P < .001). Pretreatment arthritis and/or rheumatism (relative risk [RR], 1.58; 95% CI, 1.06-2.35 [P = .023]) and regimens containing paclitaxel (RR, 2.88; 95% CI, 1.72-4.83 [P < .0001]) were associated with higher CIPN severity. Being married (RR, 0.57; 95% CI, 0.37-0.887 [P = .01]) was found to be associated with lower CIPN severity. CONCLUSIONS: The discrepancy between patient-reported and clinician-assessed CIPN underscores the need for both patient and clinician perspectives regarding this common, dose-limiting, and potentially disabling side effect of chemotherapy. Cancer 2019;125:2945-2954.

show abstract

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

Cited by 40 publications

References 25 publications

Chemotherapy-Induced Neuropathy in Cancer Survivors

Chemotherapy-Induced Neuropathy in Cancer Survivors

Pharmacogenetic Discovery in CALGB (Alliance) 90401 and Mechanistic Validation of a VAC14 Polymorphism that Increases Risk of Docetaxel-Induced Neuropathy

Patient‐reported and clinician‐reported chemotherapy‐induced peripheral neuropathy in patients with early breast cancer: Current clinical practice

Contact Info

Product

Resources

About