Genetic associations with taxane-induced neuropathy by a genome-wide association study (GWAS) in E5103.

Schneider, B. P.; Li, L.; Miller, Kurt W.; Flockhart, D.; Radovich, Milan; Hancock, Bradley A.; Kassem, Nawal; Foroud, Tatiana; Koller, Daniel L.; Badve, Sunil; Li, Z.; Partridge, A. H.; O’Neill, Anne; Sparano, J. A.; Dang, Chau T.; Northfelt, Donald W.; Smith, Mary Lou; Railey, Elda; Sledge, G. W.

doi:10.1200/jco.2011.29.15_suppl.1000

Cited by 43 publications

(32 citation statements)

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“…Reported rates of taxane-related sensory neuropathy (TRSN) are variable depending on factors such as the dose of taxane given, concomitant neurotoxic drugs, and preexisting comorbidities. The prevalence of National Cancer Institute common toxicity criteria for adverse events (NCI CTCAE) grade 2 neuropathy is 50% to 80% in patients with stage I to III breast cancer (2)(3)(4) whereas the prevalence of grade 3 or grade 4 neuropathy is 5% to 30% (2,5). Longer-term neurotoxicity complications (beyond 2 years postchemotherapy) have also been reported (6).…”

Section: Introductionmentioning

confidence: 96%

Replication of Genetic Polymorphisms Reported to Be Associated with Taxane-Related Sensory Neuropathy in Patients with Early Breast Cancer Treated with Paclitaxel

Abraham

Guo

Dorling

et al. 2014

Clinical Cancer Research

100

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Purpose: Associations between taxane-related sensory neuropathy (TRSN) and single-nucleotide polymorphisms (SNP) have previously been reported, but few have been replicated in large, independent validation studies. This study evaluates the association between previously investigated SNPs and TRSN, using genotype data from a study of chemotherapy-related toxicity in patients with breast cancer.Experimental Design: We investigated 73 SNPs in 50 genes for their contribution to TRSN risk, using genotype data from 1,303 European patients. TRSN was assessed using National Cancer Institute common toxicity criteria for adverse events classification. Unconditional logistic regression evaluated the association between each SNP and TRSN risk (primary analysis). Cox regression analysis assessed the association between each SNP and cumulative taxane dose causing the first reported moderate/severe TRSN (secondary analysis). The admixture likelihood (AML) test, which considers all SNPs with a prior probability of association with TRSN together, tested the hypothesis that certain SNPs are truly associated.Results: The AML test provided strong evidence for the association of some SNPs with TRSN (P ¼ 0.023). The two most significantly associated SNPs were rs3213619(ABCB1) [OR ¼ 0.47; 95% confidence interval (CI), 0.28-0.79; P ¼ 0.004] and rs9501929(TUBB2A) (OR ¼ 1.80; 95% CI, 1.20-2.72; P ¼ 0.005). A further 9 SNPs were significant at P-value 0.05.Conclusion: This is currently the largest study investigating SNPs associated with TRSN. We found strong evidence that SNPs within genes in taxane pharmacokinetic and pharmacodynamic pathways contribute to TRSN risk. However, a large proportion of the inter-individual variability in TRSN remains unexplained. Further validated results from GWAS will help to identify new pathways, genes, and SNPs involved in TRSN susceptibility. Clin Cancer Res; 20(9); 2466-75. Ó2014 AACR.

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Section: Introductionmentioning

confidence: 96%

Replication of Genetic Polymorphisms Reported to Be Associated with Taxane-Related Sensory Neuropathy in Patients with Early Breast Cancer Treated with Paclitaxel

Abraham

Guo

Dorling

et al. 2014

Clinical Cancer Research

100

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“…In summary, neurons conducting pain and touch sensations in the distal extremities are most vulnerable to taxanes, to other antitubulin agents, and to platinums (11). Pharmacogenomic studies are seeking to explain an individual susceptibility to severe taxane neuropathy (12)(13)(14)(15). The current analysis focuses on specific taxane clinical data on neuropathy from large randomized clinical trials.…”

Section: Description Of Taxane Neurotoxicitymentioning

confidence: 99%

Defining Risks of Taxane Neuropathy: Insights from Randomized Clinical Trials

Kudlowitz

2013

Clinical Cancer Research

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Sensory neuropathy is a common but difficult to quantify complication encountered during treatment of various cancers with taxane-containing regimens. Docetaxel, paclitaxel, and its nanoparticle albuminbound formulation have been extensively studied in randomized clinical trials comparing various dose and schedules for the treatment of breast, lung, and ovarian cancers. This review highlights differences in extent of severe neuropathies encountered in such randomized trials and seeks to draw conclusions in terms of known pharmacologic factors that may lead to neuropathy. This basic knowledge provides an essential background for exploring pharmacogenomic differences among patients in relation to their susceptibility of developing severe manifestations. In addition, the differences highlighted may lead to greater insight into drug and basic host factors (such as age, sex, and ethnicity) contributing to axonal injury from taxanes.

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“…Additionally, those patients who are obese and older age are at greater risk (Rowinsky et al 1993a , b ). Finally, recent data suggest that African American patients might also be at a markedly higher risk for paclitaxel induced CIPN (Schneider et al 2011 ). Thus, special attention must be paid to these patient populations when preparing to treat them with a potentially neurotoxic agent.…”

Section: Overviewmentioning

confidence: 96%

“…Attempts at additional confi rmation of these data may soon be on the way. Several other GWAS have been completed across the Cooperative group system that might allow for validation of the existing fi ndings, including that from the SWOG-0221 trial and ECOG-5103 trial (Schneider et al 2011 ). This could provide an amazing opportunity to perform a meta-analysis across these trials; and this has been proposed.…”

Section: Future Directionsmentioning

confidence: 97%

Symptoms: Chemotherapy-Induced Peripheral Neuropathy

Schneider

Hershman

Loprinzi

2015

Advances in Experimental Medicine and Biology

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Chemotherapy-induced peripheral neuropathy (CIPN) is a problematic, treatment-induced toxicity that has the potential to impact quality of life and limit the doses of curative intent therapy. This therapy-induced side effect is one of the most troublesome in oncology clinical practices, considering the morbidity, the frequency, and the potential irreversibility of this problem. Patients with breast cancer are particularly impacted by this side effect as multiple agents commonly used for this disease can cause neuropathy. In this chapter, we provide an overview of CIPN, including: clinical predictors, frequency, and its impact on quality of life. Further, we highlight the pathophysiology and review the literature to date for agents designed to prevent or treat CIPN. We also highlight the most important ongoing clinical and translational research questions that hope to help better predict and prevent this toxicity. This includes optimizing the methods of assessment, using host specific factors (Race and genetics) to predict those more likely to experience CIPN, and determining how CIPN might impact clinical decisions toward therapy.

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Genetic associations with taxane-induced neuropathy by a genome-wide association study (GWAS) in E5103.

Cited by 43 publications

References 0 publications

Replication of Genetic Polymorphisms Reported to Be Associated with Taxane-Related Sensory Neuropathy in Patients with Early Breast Cancer Treated with Paclitaxel

Replication of Genetic Polymorphisms Reported to Be Associated with Taxane-Related Sensory Neuropathy in Patients with Early Breast Cancer Treated with Paclitaxel

Defining Risks of Taxane Neuropathy: Insights from Randomized Clinical Trials

Symptoms: Chemotherapy-Induced Peripheral Neuropathy

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