taxane and Peripheral-Nervous-System-Diseases

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common dose-limiting toxicity of cancer treatment causing functional impairment and impacting quality of life. Effective prevention and treatment of CIPN are lacking, and CIPN risk factors remain ill-defined. Metabolic syndrome and associated conditions have emerged as potential risk factors, due to their high prevalence and independent association with nerve dysfunction. This systematic review aimed to investigate the association between these common metabolic-lifestyle factors and CIPN.. Searches were undertaken using Medline, Embase, CINAHL, Scopus, and Web of Science databases, with additional studies identified from bibliographic references cited by original and review articles. Articles that analyzed metabolic-lifestyle risk factors associated with CIPN for patients treated with platinum- or taxane-based chemotherapy were included.. Searches identified 6897 titles; 44 articles had full text review, with 26 studies included. Overall incidence of neuropathy ranged from 16.9 to 89.4%. Obesity had the most consistent patient-oriented evidence as a risk factor for CIPN, with moderate evidence suggesting diabetes did not increase CIPN incidence or severity. A limited number of studies supported an association with low physical activity and greater CIPN risk.. Comorbidities and lifestyle factors, particularly obesity and low physical activity, may contribute to the development of CIPN. The implementation of sensitive outcome measures in large-scale clinical trials is required to further elucidate CIPN risk factors and evaluate if changes in lifestyle would improve long-term CIPN outcomes for cancer survivors.. Better understanding of CIPN risk profiles may inform personalized medicine strategies and help elucidate pathophysiological mechanisms which could be targeted for neuroprotection.

Topics: Antineoplastic Agents; Cancer Survivors; Humans; Life Style; Neurotoxicity Syndromes; Obesity; Peripheral Nervous System Diseases; Platinum; Quality of Life; Risk Factors; Taxoids

Taxane-based chemotherapy regimens are used as first-line treatment for breast cancer. Neurotoxicity, mainly taxane-induced peripheral neuropathy (TIPN), remains the most important dose-limiting adverse event. Multiple genes may be associated with TIPN; however, the strength and direction of the association remain unclear. For this reason, we systematically reviewed observational studies of TIPN pharmacogenetic markers in breast cancer treatment. We conducted a systematic search of terms alluding to breast cancer, genetic markers, taxanes, and neurotoxicity in Ovid, ProQuest, PubMed, Scopus, Virtual Health, and Web of Science. We assessed the quality of evidence and bias profile. We extracted relevant variables and effect measures. Whenever possible, we performed random-effects gene meta-analyses and examined interstudy heterogeneity with meta-regression models and subgroup analyses. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and STrengthening the REporting of Genetic Association Studies (STREGA) reporting guidance. A total of 42 studies with 19,431 participants were included. These evaluated 262 single-nucleotide polymorphisms (SNPs) across 121 genes. We conducted meta-analyses on 23 genes with 60 SNPs (19 studies and 6246 participants). Thirteen individual SNPs (ABCB1-rs2032582, ABCB1-rs3213619, BCL6/-rs1903216, /CAND1-rs17781082, CYP1B1-rs1056836, CYP2C8-rs10509681, CYP2C8-rs11572080, EPHA5-rs7349683, EPHA6-rs301927, FZD3-rs7001034, GSTP1-rs1138272, TUBB2A-rs9501929, and XKR4-rs4737264) and the overall SNPs' effect in four genes (CYP3A4, EphA5, GSTP1, and SLCO1B1) were statistically significantly associated with TIPN through meta-analysis. In conclusion, through systematic review and meta-analysis, we found that polymorphisms, and particularly 13 SNPs, are associated with TIPN, suggesting that genetics does play a role in interindividual predisposition. Further studies could potentially use these findings to develop individual risk profiles and guide decision making.

Topics: Breast Neoplasms; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP3A; Female; Genetic Markers; Humans; Liver-Specific Organic Anion Transporter 1; Neurotoxicity Syndromes; Paclitaxel; Peripheral Nervous System Diseases; Pharmacogenetics; Polymorphism, Single Nucleotide; Taxoids

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect that largely remains an unresolved clinical issue, leading to long-term morbidity. This meta-analysis aimed to evaluate the efficacy and safety of Ganglioside-monosialic acid (GM1) in preventing CIPN.. Systematic literature searches of PubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were performed to identify randomized controlled trials and cohort studies that evaluated the efficacy of GM1 for preventing CIPN. Conventional meta-analysis with a random-effects model and trial sequential analysis (TSA) were performed.. A total of five studies involving 868 participants were included. The results showed that GM1 did not reduce the overall incidence of grade ≥ 2 CIPN when the common terminology criteria for adverse events (CTCAE) was used (OR 0.34, 95% CI 0.34-1.11). Subgroup analyses showed that GM1 could not reduce the risk of CTCAE grade ≥ 2 CIPN (OR 0.63, 95% CI 0.35-1.13) and neurotoxicity criteria of Debiopharm (DEB-NTC) grade ≥ 2 CIPN (OR 0.25, 95% CI 0.01-7.10) in oxaliplatin-treated patients, despite that GM1 was associated with a reduced risk of CTCAE grade ≥ 2 CIPN in the taxane subgroup of one study (OR 0.003, 95% CI 0.00-0.05). These results were confirmed by the sub-analysis of randomized controlled trials (RCTs). In TSA, the z-curve for the taxane subgroup crossed the upper trial sequential monitoring boundary (TSMB) but do not reach the required information size (RIS). The z-curves for the oxaliplatin subgroup remained in the nonsignificant area and did not reach the RIS. Further, GM1 did not influence the rate of response to chemotherapy and CTCAE grade ≥ 2 adverse events such as fatigue, nausea, diarrhea, and rash.. GM1 seemed to be well-tolerated and did not influence the anti-cancer effects of chemotherapeutic agents. Although the data did not confirm the effectiveness of GM1 in preventing oxaliplatin-induced peripheral neuropathy, GM1 might be able to prevent taxane-induced peripheral neuropathy. More studies are required in different ethnic populations receiving taxane-based chemotherapy to confirm these findings.

Topics: Antineoplastic Agents; Bias; Bridged-Ring Compounds; G(M1) Ganglioside; Humans; Oxaliplatin; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic; Response Evaluation Criteria in Solid Tumors; Retrospective Studies; Taxoids

Taxane-induced peripheral neurotoxicity (TIPN) is the most common non-hematological side effect of taxane-based chemotherapy, and may result in dose reductions and discontinuations, having as such a detrimental effect on patients' overall survival. Epothilones share similar mechanism of action with taxanes. The typical TIPN clinical presentation is mainly comprised of numbness and paresthesia, in a stocking-and-glove distribution and may progress more proximally over time, with paclitaxel being more neurotoxic than docetaxel. Motor and autonomic involvement is less common, whereas an acute taxane-induced acute pain syndrome is frequent. Patient reported outcomes questionnaires, clinical evaluation, and instrumental tools offer complementary information in TIPN. Its electrodiagnostic features include reduced/abolished sensory action potentials, and less prominent motor involvement, in keeping with a length-dependent, axonal dying back predominately sensory neuropathy. TIPN is dose-dependent and may be reversible within months after the end of chemotherapy. The single and cumulative delivered dose of taxanes is considered the main risk factor of TIPN development. Apart from the cumulative dose, other risk factors for TIPN include demographic, clinical, and pharmacogenetic features with several single-nucleotide polymorphisms potentially linked with increased susceptibility of TIPN. There are currently no neuroprotective strategies to reduce the risk of TIPN, and symptomatic treatments are very limited. This review critically examines the pathogenesis, incidence, risk factors (both clinical and pharmacogenetic), clinical phenotype and management of TIPN.

Topics: Antineoplastic Agents; Bridged-Ring Compounds; Clinical Trials as Topic; Duloxetine Hydrochloride; Epothilones; Humans; Neurotoxicity Syndromes; Peripheral Nervous System Diseases; Prospective Studies; Serotonin and Noradrenaline Reuptake Inhibitors; Taxoids; Treatment Outcome; Tubulin Modulators

Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect frequently caused by taxanes. Because the mechanisms underlying CIPN pathogenesis remain to be fully elucidated, there is no indicator for objective diagnosis like a biomarker. In addition, treatment options for CIPN is still unsatisfactory. We have previously demonstrated that paclitaxel preferentially impair myelin-forming Schwann cells, and consequently induce dedifferentiation and demyelination of Schwann cells. Recently, in a paclitaxel CIPN model mouse, we found that an inflammatory factor is released from dedifferentiated Schwann cells in the mouse sciatic nerve into the blood, highly correlated with the on-set of mechanical hypersensitivity. On the other hand, considering our previous findings, it seems that some drugs, which supply newly formed mature Schwann cells at the sites of demyelinated lesions, may be a new beneficial therapy for taxane-induced peripheral neuropathy. In this review, we will introduce our findings about new therapeutic drug candidate for taxane-related CIPN based on this concept, and plasma biomarker to detect CIPN on-set and progression.

Topics: Animals; Antineoplastic Agents; Biomarkers; Bridged-Ring Compounds; Mice; Peripheral Nervous System Diseases; Schwann Cells; Taxoids

One in 2 Canadians is expected to acquire cancer in their lifetime. Many cancers, including breast, ovarian, and lung cancer, are treated using taxane chemotherapy with curative intent. A major adverse effect with the use of taxane chemotherapeutic agents is taxane-induced peripheral neuropathy (TIPN). Both positive (spontaneous pain, heightened sensitivity with light touch, tingling, itching, burning) and negative (loss of touch, loss of hot/cold sensations, and loss of pain) sensory symptoms can be experienced in the hands and feet and worsen with increasing dose and treatment duration. The pathophysiology of TIPN is still unknown but likely involves multiple mechanisms, including microtubule impairment, neuroimmune and inflammatory changes, ion channel remodeling, impaired mitochondrial function, and genetic predisposition. This review highlights current theories on the pathophysiology for TIPN, the cellular responses thought to maintain neuropathic pain, and the growing support for exercise in the treatment and prevention of peripheral neuropathy and neuropathic pain in both animal and human models.

Topics: Antineoplastic Agents; Bridged-Ring Compounds; Exercise Therapy; Humans; Neoplasms; Neuralgia; Peripheral Nervous System Diseases; Taxoids

Taxane containing chemotherapy extends survival for breast cancer patients. However, taxane-induced peripheral neuropathy (TIPN) cannot be predicted, prevented or effectively treated. Using genome-wide analyses, we sought to identify common risk variants for TIPN.. Women with high-risk breast cancer enrolled in SWOG 0221 were genotyped using the Illumina 1M chip. Genome-wide analyses were performed in relation to ≥grade 3 Common Terminology Criteria for Adverse Events (CTCAE) neuropathy in European and African Americans. Data were meta-analyzed with GW associations of CTCAE ≥grade 3 versus

Topics: Black or African American; Breast Neoplasms; Bridged-Ring Compounds; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomics; Genotype; Humans; Peripheral Nervous System Diseases; Polymorphism, Single Nucleotide; Taxoids; White People

In this review, we discuss the plight of Alice, a patient with advanced nonsmall cell lung cancer (NSCLC) who struggles with taxane-related peripheral neuropathy (PN). Using this unique point of view helps us to appreciate the implications of PN on daily activities as well as the difficulty in decision-making regarding continuation of treatment. In addition, published reports of phase 3 trials are reviewed to identify the incidence and severity of chemotherapy-induced PN as well as the assessment tools used in these studies.. A literature review spanning the years 1998-2012 was performed. Phase 3 studies and a meta-analysis of taxane-based therapy in advanced NSCLC were selected for review for their findings regarding the incidence and severity of chemotherapy-induced PN.. In total, 16 phase 3 studies and 1 meta-analysis were reviewed. Use of grading scales and PN assessment tools was inconsistent across the studies, and some studies did not report PN at all.. The true incidence and severity of chemotherapy-induced PN in clinical trials may be masked by nonstandardized reporting; thus, a more standardized approach to grading, assessing, and reporting PN in clinical trials is greatly needed to allow for appropriate comparisons across studies. Understanding chemotherapy-induced PN from the patient's perspective as well as the development of PN at the clinical trial level will help health care providers anticipate the development of PN and improve their ability to manage it.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Neuralgia; Peripheral Nervous System Diseases; Restless Legs Syndrome; Taxoids

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 albumin-bound 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.

Topics: Axons; Bridged-Ring Compounds; Docetaxel; Drug-Related Side Effects and Adverse Reactions; Humans; Nanoparticles; Neoplasms; Paclitaxel; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic; Taxoids

The two commercially available taxanes (paclitaxel and docetaxel) are widely employed in standard oncologic practice. Toxicity of the agents includes bone marrow suppression (principally neutropenia), complete alopecia, and hypersensitivity reactions. While both drugs can cause neurotoxicity and myalgias/arthralgias, this is a greater clinical concern with paclitaxel. Docetaxel can be associated with the development of significant fluid retention (e.g., edema, ascites, pleural effusions), the incidence and severity of which appear to be limited by prophylactic treatment with corticosteroids both before and after each treatment. If patients are monitored closely (e.g., for hypersensitivity reactions, bone marrow suppression) the taxanes have a favorable side effect profile, and it is currently uncommon for treatment to be discontinued because of the development of excessive toxicity.

Topics: Antineoplastic Agents, Phytogenic; Arthralgia; Bridged-Ring Compounds; Docetaxel; Drug Hypersensitivity; Humans; Neutropenia; Paclitaxel; Peripheral Nervous System Diseases; Taxoids; Thrombocytopenia

This study investigated whether there are pharmacogenomic markers predictive of chemotherapy induced peripheral neuropathy (CIPN) as a result of taxane-based chemotherapy.. Patients were enrolled from August 2020 to November 2020 in a prospective, case-control trial evaluating pharmacogenetic predictors of CIPN. All women were treated with at least 3 cycles of taxane-based chemotherapy for histologically confirmed gynecologic malignancies. Buccal saliva samples were used to test for 32 drug metabolism variations. All testing was performed by ⍺LPHA-GENOMIX laboratories. Fisher's Exact test was used to assess for event differences of categorical variables.. Of 102 enrolled patients, 58%, 28%, and 14% had ovarian, endometrial, or cervical cancers, respectively. The median age was 67, 72% were Caucasian and 25% were African American. 16% of patients were treated with 3-4 cycles, 57% received 5-7 cycles, and 27% received 8 or more cycles of chemotherapy that included paclitaxel. Grade 2 CIPN was experienced by 51 patients. There was no difference in age, race, disease site, or number of chemotherapy cycles (p > 0.05) between those who did or did not develop CIPN. CYP2D6 genotype (p = 0.009) and CYP3A5 genotype (p = 0.023) had different frequencies among those with and without CIPN. Patients classified as having poor or intermediate function of CYP2D6 had increased risk of CIPN (OR 1.63, 95% CI 1.04-2.57, p = 0.026). There was no difference in CYP2D6 phenotype by race (p = 0.29). No patients with normal function of CYP3A5 developed CIPN. There were no Caucasians with normal function of CYP3A5, but 28% of African Americans had normal CYP3A5 function (p < 0.001).. Pharmacogenomics appear associated with the development of CIPN and may be able to help personalize treatment decision making.

Topics: Aged; Antineoplastic Agents; Breast Neoplasms; Case-Control Studies; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Female; Genital Neoplasms, Female; Humans; Peripheral Nervous System Diseases; Pharmacogenetics; Prospective Studies; Taxoids

To compare the effectiveness of acupuncture alone or with additional integrative oncology modalities for taxane-induced peripheral neuropathy-related symptoms in patients with gynecological and breast cancer.. The study was a prospective evaluation of patients undergoing twice-weekly treatments with either acupuncture alone (single-modality, group A) or with additional manual-movement and mind-body therapies (multimodality, group B), for 6 weeks. Symptom severity was assessed at baseline, 6 weeks, and 9 weeks using the Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) tool; and von Frey perception thresholds. Additional symptoms were also assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the Measure Yourself Concerns and Wellbeing (MYCaW) study tool.. For the 120 participants (60 in each study arm), baseline to 6-week scores were similar in both groups for improved FACT-Tax physical wellbeing and scores for hand numbness/tingling; EORTC physical functioning and global health status; and MYCaW scores. FACT-Tax taxane subscales and scores for foot numbness/tingling improved only in group A (p=0.038), while emotional wellbeing FACT-Tax (p=0.02) and EORTC pain (p=0.005) improved only in group B. Group B showed greater improvement for FACT-Tax neuropathy-related concerns than group A at 24 hours (p=0.043) and 7 days (p=0.009) after the first treatment.. Acupuncture alone or with additional integrative oncology modalities may help reduce neuropathy-related symptoms. The single-modality group demonstrated greater improvement for foot numbness/tingling, and the multimodality group demonstrated improvement for pain and improved emotional wellbeing and neuropathy-related concerns in the first week of treatment.. NCT03290976.

Topics: Acupuncture Therapy; Humans; Hypesthesia; Integrative Oncology; Pain; Peripheral Nervous System Diseases; Quality of Life; Surveys and Questionnaires; Taxoids

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of taxane treatment and can significantly affect patient quality of life. Currently, there are no effective treatments to alleviate symptoms of CIPN; thus, starting with prevention steps in high-risk patients is considered advantageous. However, for these prevention steps to be applicable to all patients, their side effects or accompanying discomforts should be minimal, and the intervention cost-effective. Compression therapy can be considered a prevention intervention, and using surgical gloves is feasible and cost-effective (approximately $0.6 per pair). Although previous studies on compression therapy using surgical gloves have reported decreased incidence of PN, these studies were non-randomized, limited to nab-paclitaxel treatment, and involved the use of small gloves, which may have caused discomfort. Therefore, this study aimed to assess the preventive effects of compression therapy using normal-sized surgical gloves on CIPN in patients treated with paclitaxel.. This clinical trial is designed to evaluate the preventive effects of compression therapy using surgical gloves on CIPN in women with stage II-III breast cancer who received paclitaxel chemotherapy for at least 12 weeks. This multicenter, randomized-controlled, open-label study will be conducted in six academic hospitals. Patients with medication or a medical history related to neuropathy or hand disease will be excluded. The primary outcome will be the preventive effect of compression therapy using surgical gloves, measured based on changes in the neurotoxicity component of the Functional Assessment of Cancer Therapy-Taxane questionnaire. Furthermore, we will assess the National Cancer Institute's Common Terminology Criteria for Adverse Events grade of CIPN after 6 months. Notably, the estimated sample size, based on a p-value < 0.025 and statistical power of 0.9, will consist of 104 patients (52 per group), accounting for a 10% sample loss.. This intervention can be easily implemented in clinical practice and may serve as a preventive strategy for CIPNs with strong patient adherence. If successful, this intervention could improve the quality of life and treatment adherence in patients receiving chemotherapy that can induce PN, extending beyond paclitaxel treatment alone.. ClinicalTrials.gov, NCT05771974; Registered on March 16, 2023.

Topics: Antineoplastic Agents; Breast Neoplasms; Female; Gloves, Surgical; Humans; Paclitaxel; Peripheral Nervous System Diseases; Quality of Life; Taxoids

Chemotherapy-induced peripheral neuropathy (CIPN) is an important clinical challenge that threatens patients' quality of life. This sub-study of the ABROAD trial investigated the influence of single nucleotide polymorphisms (SNPs) on CIPN, using genotype data from a randomized study to determine the optimal dose of a 3-week-cycle regimen of nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Patients with HER2-negative MBC were randomly assigned to three doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2). Five SNPs (EPHA4-rs17348202, EPHA5-rs7349683, EPHA6-rs301927, LIMK2-rs5749248, and XKR4-rs4737264) were analyzed based on the results of a previous genome-wide association study. Per-allele SNP associations were assessed by a Cox regression to model the cumulative dose of nab-PTX up to the onset of severe or worsening sensory neuropathy. A total of 141 patients were enrolled in the parent study; 91(65%) were included in this sub-study. Worsening of CIPN was significantly greater in the cases with XKR4 AC compared to those with a homozygote AA (HR 1.86, 95%CI: 1.00001-3.46, p=0.049). There was no significant correlation of CIPN with any other SNP. A multivariate analysis showed that the cumulative dose of nab-PTX was most strongly correlated with CIPN (p<0.01).

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Genome-Wide Association Study; Humans; Peripheral Nervous System Diseases; Polymorphism, Single Nucleotide; Quality of Life; Taxoids

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of chemotherapy. Several trials have evaluated the protective effect of vitamin E in preventing CIPN with controversial results. This study aims to outline the role of vitamin E in preventing CIPN.. A prospective phase II, open-label randomized controlled study was conducted in patients receiving taxane-based chemotherapy in Ain Shams University Hospitals, using vitamin E at a dose of 400 mg twice daily. The primary endpoint was the incidence of grade ≥ 2 sensory neuropathy according to CTCAE v 5.0 in each treatment arm. Secondary endpoints include time to onset and the duration of grade ≥ 2 sensory neuropathy.. A total of 140 patients were randomized between the control and vitamin E arms. There was no difference in the incidence of grade ≥ 2 sensory neuropathy between the two arms (25.7% in each arm; P = 1.0), as well as the time to onset of neuropathy (P = 0.24). However, there was a statistically significant difference between the 2 arms as regards the duration of neuropathy. The median duration was 12.5 vs. 5 weeks in the control and vitamin E arms respectively (P = 0.01).. Our study did not demonstrate a protective role of vitamin E in decreasing the incidence of CIPN in patients receiving taxane-based chemotherapy. However, the recovery from CIPN was much better as compared to the control arm, which may indicate a role for vitamin E in decreasing the duration and severity of CIPN.

Topics: Antineoplastic Agents; Antioxidants; Bridged-Ring Compounds; Case-Control Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Peripheral Nervous System Diseases; Prognosis; Prospective Studies; Taxoids; Vitamin E

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Exercise Therapy; Female; Follow-Up Studies; Humans; Middle Aged; Neuralgia; Neurological Rehabilitation; Outcome Assessment, Health Care; Peripheral Nervous System Diseases; Single-Blind Method; Taxoids

Taxane-induced peripheral neuropathy (TIPN) is a dose-limiting adverse effect. Ganglioside-monosialic acid (GM1) functions as a neuroprotective factor. We assessed the effects of GM1 on the prevention of TIPN in breast cancer patients.. We conducted a randomized, double-blind, placebo-controlled trial including 206 patients with early-stage breast cancer planning to receive taxane-based adjuvant chemotherapy with a follow-up of more than 1 year. Subjects were randomly assigned to receive GM1 (80 mg, day -1 to day 2) or placebo. The primary endpoint was the Functional Assessment of Cancer Treatment Neurotoxicity subscale score after four cycles of chemotherapy. Secondary endpoints included neurotoxicity evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and the Eastern Cooperative Oncology Group neuropathy scale. All statistical tests were two-sided.. In 183 evaluable patients, the GM1 group reported better mean Functional Assessment of Cancer Treatment Neurotoxicity subscale scores than patients in the placebo group after four cycles of chemotherapy (43.27, 95% confidence interval [CI] = 43.05 to 43.49 vs 34.34, 95% CI = 33.78 to 34.89; mean difference = 8.96, 95% CI = 8.38 to 9.54, P < .001). Grade 1 or higher peripheral neurotoxicity in Common Terminology Criteria for Adverse Events v4.0 scale was statistically significantly lower in the GM1 group (14.3% vs 100.0%, P < .001). Additionally, the GM1 group had a statistically significantly lower incidence of grade 1 or higher neurotoxicity assessed by Eastern Cooperative Oncology Group neuropathy scale sensory neuropathy (26.4% vs 97.8%, P < .001) and motor neuropathy subscales (20.9% vs 81.5%, P < .001).. The treatment with GM1 resulted in a reduction in the severity and incidence of TIPN after four cycles of taxane-containing chemotherapy in patients with breast cancer.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Female; Follow-Up Studies; Gangliosides; Humans; N-Acetylneuraminic Acid; Neuroprotective Agents; Peripheral Nervous System Diseases; Taxoids

Over half of all cancer patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN), which includes numbness, tingling, pain, cold sensitivity, and motor impairment in the hands and feet. CIPN is a dose-limiting toxicity, potentially increasing mortality. There are no FDA-approved drugs to treat CIPN, and behavioral interventions such as exercise are promising yet understudied. This secondary analysis of our nationwide phase III randomized controlled trial of exercise for fatigue examines (1) effects of exercise on CIPN symptoms, (2) factors that predict CIPN symptoms, and (3) factors that moderate effects of exercise on CIPN symptoms.. Cancer patients (N = 355, 56 ± 11 years, 93% female, 79% breast cancer) receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy were randomized to chemotherapy or chemotherapy plus Exercise for Cancer Patients (EXCAP©®). EXCAP is a standardized, individualized, moderate-intensity, home-based, six-week progressive walking and resistance exercise program. Patients reported CIPN symptoms of numbness and tingling and hot/coldness in hands/feet (0-10 scales) pre- and post-intervention. We explored baseline neuropathy, sex, age, body mass index, cancer stage, and cancer type as possible factors associated with CIPN symptoms and exercise effectiveness.. Exercise reduced CIPN symptoms of hot/coldness in hands/feet (-0.46 units, p = 0.045) and numbness and tingling (- 0.42 units, p = 0.061) compared to the control. Exercise reduced CIPN symptoms more for patients who were older (p = 0.086), male (p = 0.028), or had breast cancer (p = 0.076).. Exercise appears to reduce CIPN symptoms in patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy. Clinicians should consider prescribing exercise for these patients.. Clinical Trials.gov , # NCT00924651, http://www.clinicaltrials.gov .

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Exercise Therapy; Female; Humans; Male; Middle Aged; Neoplasm Staging; Neoplasms; Organoplatinum Compounds; Peripheral Nervous System Diseases; Taxoids; Vinca Alkaloids

The current experimental study aimed to evaluate the effectiveness of reflexology on the management of symptoms and functions of chemotherapy-induced peripheral neuropathy (CIPN) in cancer patients.. This study was conducted as a randomized controlled trial in 60 patients (30 experimental and 30 control patients) who had chemotherapy-induced Grade II-IV peripheral neuropathy complaints from July 2013 to November 2015. Data were collected using the patient identification form, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy (EORTC-CIPN-20) form, and BPI (used for related chemotherapy-induced peripheral neuropathy symptoms).. The majority of the patients were being treated for gastrointestinal or breast cancer and were primarily receiving Eloxatine- or taxane-based treatment. It was found that reflexology applications did not lead to differences in either group in terms of peripheral neuropathy severity and incidence (p > 0.05) and only led to improvement in sensory functions in the experimental group (p < 0.05).. It was determined that reflexology is not an effective method in the management of patients' activity levels, walking ability etc. and motor, autonomic functions related CIPN, but reflexology is effective method in the management of patients' sensory functions related CIPN. Key Words: Peripheral neuropathy, reflexology, chemotherapy, EORTC QLQ-CIPN-20, BPI.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Female; Gastrointestinal Neoplasms; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peripheral Nervous System Diseases; Pilot Projects; Quality of Life; Reflexotherapy; Surveys and Questionnaires; Taxoids

Capecitabine is an approved standard therapy for anthracycline- and taxane-pretreated locally advanced or metastatic breast cancer (BC). Vinflunine has demonstrated single-agent activity in phase II studies in this setting and activity and tolerability when combined with capecitabine. We compared the combination of vinflunine plus capecitabine (VC) with single-agent capecitabine.. Patients with locally recurrent/metastatic BC previously treated or resistant to an anthracycline and resistant to taxane therapy were randomly assigned to either vinflunine (280 mg/m2, day 1) plus oral capecitabine [825 mg/m2 twice daily (b.i.d.), days 1-14] every 3 weeks (q3w) or single-agent oral capecitabine (1250 mg/m2 b.i.d., days 1-14) q3w. The primary end point was progression-free survival (PFS) assessed by an independent review committee. The study had 90% power to detect a 30% improvement in PFS.. Overall, 770 patients were randomised. PFS was significantly longer with VC than with capecitabine alone [hazard ratio, 0.84, 95% confidence interval (CI), 0.71-0.99; log-rank P = 0.043; median 5.6 versus 4.3 months, respectively]. Median overall survival was 13.9 versus 11.7 months with VC versus capecitabine alone, respectively (hazard ratio, 0.98; 95% CI, 0.83-1.15; log-rank P = 0.77). No difference in quality of life was observed between the two treatment arms. The most common adverse events (NCI CTCAE version 3.0) in the combination arm were haematological and gastrointestinal. Grade 4 neutropenia was more frequent with VC (12% versus 1% with capecitabine alone); febrile neutropenia occurred in 2% versus 0.5%, respectively. Hand-foot syndrome was less frequent with VC (grade 3: 4% versus 19% for capecitabine alone). Peripheral neuropathy was uncommon in both arms (grade 3: 1% versus 0.3%).. Vinflunine combined with capecitabine demonstrated a modest improvement in PFS and an acceptable safety profile compared with capecitabine alone in patients with anthracycline- and taxane-pretreated locally recurrent/metastatic BC.. NCT01095003.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Chemotherapy-Induced Febrile Neutropenia; Drug Resistance, Neoplasm; Female; Hand-Foot Syndrome; Humans; Middle Aged; Neoplasm Recurrence, Local; Neurotoxicity Syndromes; Peripheral Nervous System Diseases; Progression-Free Survival; Quality of Life; Survival Analysis; Taxoids; Vinblastine

To investigate the effect of electro-acupuncture (EA) as a non-pharmacological intervention to prevent or reduce chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer patients undergoing chemotherapy of taxane. Women with stage I-III breast cancer scheduled to receive taxane therapy were randomized to receive a standardized protocol of 12 true or sham EA (SEA) weekly treatments concurrent with taxane treatment. Subjects completed the Brief Pain Inventory-Short Form (BPI-SF), Functional Assessment of Cancer Therapy-Taxane neurotoxicity subscale (FACT-NTX), and other assessments at baseline and weeks 6, 12, and 16. A total of 180 subjects were screened, 63 enrolled and 48 completed week 16 assessments. Mean age was 50 with 25 % white, 25 % black, and 43 % Hispanic; 52 % had no prior chemotherapy. At week 12, both groups reported an increase in mean BPI-SF worst pain score, but no mean differences were found between groups (SEA 2.8 vs. EA 2.6, P = .86). By week 16, the SEA group returned to baseline, while the EA group continued to worsen (SEA 1.7 vs. EA 3.4, P = .03). The increase in BPI-SF worst pain score was 1.62 points higher in the EA group than in the SEA group at week 16 (P = .04). In a randomized, sham-controlled trial of EA for prevention of taxane-induced CIPN, there were no differences in pain or neuropathy between groups at week 12. Of concern, subjects on EA had a slower recovery than SEA subjects. Future studies should focus on EA for treatment as opposed to prevention of CIPN.

Topics: Adult; Aged; Breast Neoplasms; Bridged-Ring Compounds; Double-Blind Method; Electroacupuncture; Female; Humans; Middle Aged; Peripheral Nervous System Diseases; Pilot Projects; Taxoids; Treatment Outcome

Lafutidine, an antagonist of histamine H2-receptor, has gastroprotective activity associated with activation of capsaicin-mediated sensory nerves. The objective of this study was to investigate the efficacy of lafutidine for the treatment of taxane-induced peripheral neuropathy in patients with gynecological malignancies.. Twenty patients with taxane-induced peripheral neuropathy during the treatment of gynecological malignancy were enrolled in this study. After obtaining their informed consent, lafutidine (20mg per day) was administered orally, the efficacy of which was assessed according to the Patient Neurotoxicity Questionnaire item 1.. Significant, moderate, slight, and no effects were observed in four, five, five, and six patients, respectively. The efficacy including significant and moderate effect was observed in nine (45%) of the 20 patients (95% confidence interval, 25.8%-65.8%). No adverse effects due to lafutidine were observed.. This pilot study supports the relatively high efficacy of lafutidine for the treatment of taxane-induced peripheral neuropathy. Further prospective studies are warranted.

Topics: Acetamides; Aged; Aged, 80 and over; Antineoplastic Agents; Bridged-Ring Compounds; Female; Genital Neoplasms, Female; Histamine H2 Antagonists; Humans; Middle Aged; Peripheral Nervous System Diseases; Piperidines; Pyridines; Taxoids

Effective treatment options for patients with metastatic breast cancer pretreated with or resistant to anthracyclines and taxanes are limited. Ixabepilone has single-agent activity in these patients and has demonstrated synergy with capecitabine in this setting. This study was designed as a prospective clinical trial to evaluate the efficacy and safety of ixabepilone plus capecitabine in both anthracycline-pretreated and resistant and taxane-resistant metastatic breast cancer of Chinese women.. Patients with measurable disease who had anthracycline and taxanes as prior neoadjuvant, adjuvant or metastatic therapy were treated with ixabepilone at 40 mg/m(2) intravenously on day 1 of 21-day cycle plus capecitabine 2,000 mg/m(2) orally on day 1 through 14 of a 21-day cycle. The primary end point was the objective response rate. The secondary end points were time to progression, overall survival, and toxicity profiles.. Twenty-one patients received 146 cycles with a median of 5 cycles (range 1-13 cycles) per patients. Fourteen patients (66.7%) had partial response, 5 patients (23.8%) had stable disease, and 2 patients (9.5%) had progressive disease. Median time to progression and duration of response were 6.2 and 6.0 months, respectively. The median overall survival was 16.7 months. Eight (38.1%) patients required dose reduction and 14 (66.7%) patients discontinued treatment for adverse effect. Grade 3/4 treatment-related events included fatigue (28.6%), peripheral sensory neuropathy (33.3%), neutropenia (61.9%), anemia (4.7%), hypokalemia (4.7%), hand and foot syndrome (19.0%) and infection (9.5%). Resolution of grade 3/4 peripheral neuropathy was reversible after a median period of 6 weeks.. Ixabepilone plus capecitabine demonstrated a clear activity and an acceptable safety profile in Chinese patients with anthracycline-pretreated/resistant and taxane-resistant metastatic breast cancer, and the majority of patients completed 6 cycles of the therapy with manageable neuropathy toxicities.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Asian People; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; China; Deoxycytidine; Disease Progression; Dose-Response Relationship, Drug; Epothilones; Female; Fluorouracil; Humans; Middle Aged; Neoplasm Metastasis; Peripheral Nervous System Diseases; Prospective Studies; Survival Rate; Taxoids; Treatment Outcome

Ixabepilone is one of the epothilones, a new class of cytotoxics, that function as microtubule-stabilizing agents. With the primary endpoint of assessing ixabepilone's response rate against metastatic gastric cancer previously treated with a taxane, we performed a multi-center phase II trial.. Patients with histologically documented metastatic gastric or gastroesophageal adenocarcinoma, who had previously received a taxane, were eligible. Patients were required to have near normal organ function, > or =18 years of age, ECOG performance status of 0 or 1. A written informed consent was obtained from all patients. Ixabepilone was administered over one hour intravenously at a dose of 50 mg/m2 every 21 days (23 patients; cohort A) and 24 subsequent patients were treated with an amended protocol schedule to receive 6 mg/m2 intravenously on days 1-5 every 21 days (cohort B).. A total of 47 patients were treated. Most patients were men with a median performance status of 1. Two of 23 patients in cohort A achieved a confirmed partial response (9%, 95% CI 1.1-28%) but none of the 24 patients in cohort B achieved a response. A higher proportion of patients in cohort A experienced Grade 3/4 toxicities compared with those in cohort B.. Ixabepilone, on a once every 21-day schedule, is modestly active against metastatic gastric cancer previously treated with a taxane. The days 1-5 every 21 days schedule had a more favorable safety profile but no activity. The results of this study suggest that once every 21-day ixabepilone schedule should be pursued further in untreated gastric or gastroesophageal adenocarcinoma patients.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Bridged-Ring Compounds; Disease Progression; Epothilones; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Peripheral Nervous System Diseases; Stomach Neoplasms; Taxoids

Taxanes form the mainstay of breast cancer therapy in the curative setting. Taxane-induced peripheral neuropathy (TIPN) is a common toxicity and confers significant morbidity with no validated therapies. Literature detailing TIPN is inconsistent in reporting its frequency, severity, risk factors, impact upon treatment course, and management practices.. A retrospective chart review was performed including 348 early-stage breast cancer patients undergoing weekly paclitaxel therapy between 2010 and 2020 in the adjuvant or neoadjuvant setting. The frequency, severity, and impact on treatment from TIPN were analyzed during treatment and at one year follow-up. Clinicopathological and patient factors were collected to identify potential risk factors.. 279 out of 348 patients (80.2%) developed TIPN of any grade. One-year follow-up was available for 232 of the original 279 TIPN patients (83.2%). Of these, 52 patients (22.4%) exhibited persisting TIPN of any grade. The presence and severity of TIPN during treatment was significantly associated with a lower median dose intensity (100% versus 82.5% for non-TIPN and all-grade TIPN respectively, p < 0.001). Neoadjuvant treatment (p = 0.038) and body surface area (BSA, p = 0.035) were independently associated with TIPN during treatment. Increased age (p < .001) and pre-treatment diabetes (p = 0.009) were associated with TIPN at one-year follow-up.. TIPN is common in breast cancer patients undergoing weekly paclitaxel therapy. TIPN results in patients receiving significantly lower dose intensity due to dose reductions and premature treatment cessation. Future prospective studies in similar cohorts are warranted, with a focus on long-term outcomes.

Topics: Breast Neoplasms; Female; Humans; Paclitaxel; Peripheral Nervous System Diseases; Prospective Studies; Retrospective Studies; Taxoids

Taxane-induced peripheral neuropathy (TIPN) is a debilitating adverse effect of cancer treatments with taxanes which may require a reduction or discontinuation chemotherapy and affect clinical and survival outcomes. A number of factors have contributed to the increasing prevalence of TIPN. Nonetheless, limited knowledge exists of potential prechemotherapy blood-based biochemical factors associated with TIPN development.. We recruited breast cancer patients at seven cancer institutions in China. Participants aged 18 years or older with stage I to III breast cancer who scheduled to undergo primary neoadjuvant and adjuvant chemotherapy with taxanes were eligible. Eligible patients underwent patient-reported neuropathy assessments using the EORTC-CIPN20 questionnaire. Patients completed the questionnaire before commencing treatment and after every cycle. For every patient, we selected the highest TIPN toxicity score for analysis since the first cycle. The posttreatment TIPN severity was compared with blood-based biochemical factors within 30 days before commencing treatment. Independent samples t tests, Mann-Whitney U tests and linear regression were used to identify blood-based and clinical associations with TIPN development.. The study included 873 breast cancer participants who received paclitaxel, docetaxel or nanoparticle albumin-bound (nab)-paclitaxel. In the whole cohort, factors associated with higher TIPN toxicity scores were higher cumulative chemotherapy dose (β = 0.005; 95% CI, 0.004 to 0.006; P < .001), lower sodium ions (β = -0.24; 95% CI, -0.39 to -0.09; P = .002) and higher chloride ions (β = 0.30; 95% CI, 0.16 to 0.44; P < .001).. The findings suggest that breast cancer patients with a higher cumulative chemotherapy dose, lower pretreatment sodium ions, and higher pretreatment chloride ions receiving taxanes should receive closer monitoring to mitigate the development of short-term and long-term TIPN.

Topics: Breast Neoplasms; Chlorides; East Asian People; Female; Humans; Paclitaxel; Peripheral Nervous System Diseases; Taxoids

Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity of taxanes for which there is no effective intervention. Genomic CIPN risk determination has yielded promising, but inconsistent results. The present study assessed the utility of a collective SNP cluster identified using novel analytics to describe taxane-associated CIPN risk.. We analyzed GWAS data derived from ECOG-5103, first identifying SNPs that were most strongly associated with CIPN using Fisher's ratio (FR). We then ranked ordered those SNPs which discriminated CIPN-positive (CIPN +) from CIPN-negative phenotypes based on their discriminatory power and developed the cluster of SNPs which provided the highest predictive accuracy using leave-one-out cross-validation (LOOCV).. Using aggregated genotype data obtained from the previously reported ECOG-5103 clinical trial (in which two different arrays were used, HumanOmniExpress (727,227 SNPs) and HumanOmni1-Quad1 (1,131,857 SNPs)), we identified a 267 SNP cluster which was associated with a CIPN + phenotype with an accuracy of 96.1%.. A cluster of SNPs was identified which prospectively discriminated patients most likely to develop symptomatic CIPN following taxane exposure as part of a breast cancer chemotherapy regimen. Validation using an independent patient cohort should be performed.

Topics: Antineoplastic Agents; Breast Neoplasms; Clinical Trials as Topic; Female; Genome-Wide Association Study; Humans; Peripheral Nervous System Diseases; Polymorphism, Single Nucleotide; Taxoids

Using GWAS data derived from a large collaborative trial (ECOG-5103), we identified a cluster of 267 SNPs which predicted CIPN in treatment-naive patients as reported in Part 1 of this study. To assess the functional and pathological implications of this set, we identified collective gene signatures were and evaluated the informational value of those signatures in defining CIPN's pathogenesis.. In Part 1, we analyzed GWAS data derived from ECOG-5103, first identifying those SNPs that were most strongly associated with CIPN using Fisher's ratio. After identifying those SNPs which differentiated CIPN-positive from CIPN-negative phenotypes, we ranked them in order of their discriminatory power to produce a cluster of SNPs which provided the highest predictive accuracy using leave-one-out cross validation (LOOCV). An uncertainty analysis was included. Using the best predictive SNP cluster, we performed gene attribution for each SNP using NCBI Phenotype Genotype Integrator and then assessed functionality by applying GeneAnalytics, Gene Set Enrichment Analysis, and PCViz.. Using aggregate data derived from the GWAS, we identified a 267 SNP cluster which was associated with a CIPN+ phenotype with an accuracy of 96.1%. We could attribute 173 genes to the 267 SNP cluster. Six long intergenic non-protein coding genes were excluded. Ultimately, the functional analysis was based on 138 genes. Of the 17 pathways identified by Gene Analytics (GA) software, the irinotecan pharmacokinetic pathway had the highest score. Highly matching gene ontology attributions included flavone metabolic process, flavonoid glucuronidation, xenobiotic glucuronidation, nervous system development, UDP glycosyltransferase activity, retinoic acid binding, protein kinase C binding, and glucoronosyl transferase activity. Gene Set Enrichment Analysis (GSEA) GO terms identified neuron-associated genes as most significant (p = 5.45e-10). Consistent with the GA's output, flavone, and flavonoid associated terms, glucuronidation were noted as were GO terms associated with neurogenesis.. The application of functional analyses to phenotype-associated SNP clusters provides an independent validation step in assessing the clinical meaningfulness of GWAS-derived data. Functional analyses following gene attribution of a CIPN-predictive SNP cluster identified pathways, gene ontology terms, and a network which were consistent with a neuropathic phenotype.

Topics: Genome-Wide Association Study; Humans; Neoplasms; Peripheral Nervous System Diseases; Polymorphism, Single Nucleotide; Taxoids

No medications are known to protect against chemotherapy-induced peripheral neuropathy (CIPN). Pre-clinical models suggest that lithium may lessen taxane-induced neuropathy. Our aim was to use clinical data to assess whether concurrent lithium usage decreased the frequency or severity of CIPN in patients receiving taxane chemotherapy.. A retrospective analysis was performed using the electronic health record at Mayo Clinic to identify all patients prescribed concurrent lithium and paclitaxel. Four controls were matched to each case based on clinical variables. Neuropathy severity was graded from available patient and clinician reports. Rates of any neuropathy, dose reduction for CIPN, and treatment discontinuation for CIPN were compared. Conditional regression analysis was performed with propensity score matching.. Six patients, receiving concurrent lithium and paclitaxel, were included in the analysis, and compared to 24 control cases. A similar number of paclitaxel cycles were administered to both groups. Any neuropathy was experienced by 33% (2/6) of patients receiving lithium and 38% (9/24) patients who did not receive lithium (p = 1.000). There was no difference in neuropathy severity (p = 0.8565), rate of chemotherapy dose reduction (17% vs. 17%, p = 1.000), or treatment discontinuation (17% vs 4%, p = 0.3655) for CIPN. In the propensity score analysis, the odds ratio for developing any neuropathy was 0.63 (95% confidence interval, 0.06 to 6.96, p = 0.7079).. Lithium does not appear to significantly lessen the risk of neuropathy for patients receiving paclitaxel.. Targeted approaches for preventing CIPN are desperately needed. Despite sound scientific rationale, the current study did not identify neuroprotective properties of lithium.

Topics: Antineoplastic Agents; Humans; Lithium; Paclitaxel; Peripheral Nervous System Diseases; Retrospective Studies; Taxoids

Paclitaxel is a widely used anticancer therapeutic. Peripheral neuropathy is the dose-limiting toxicity and negatively impacts quality of life. Rare germline gene markers were evaluated for predicting severe taxane-induced peripheral neuropathy (TIPN) in the patients of European ancestry. In addition, the impact of Cytochrome P450 (CYP) 2C8, CYP3A4, and CYP3A5 metabolizer status on likelihood of severe TIPN was also assessed.. Whole-exome sequencing analyses were performed in 340 patients of European ancestry who received a standard dose and schedule of paclitaxel in the adjuvant, randomized phase III breast cancer trial, E5103. Patients who experienced grade 3-4 (n = 168) TIPN were compared to controls (n = 172) who did not experience TIPN. For the analyses, rare variants with a minor allele frequency ≤ 3% and predicted to be deleterious by protein prediction programs were retained. A gene-based, case-control analysis using SKAT was performed to identify genes that harbored an imbalance of deleterious variants associated with increased risk of severe TIPN. CYP star alleles for CYP2C8, CYP3A4, and CYP3A5 were called. An additive logistic regression model was performed to test the association of CYP2C8, CYP3A4, and CYP3A5 metabolizer status with severe TIPN.. Cytochrome P450 oxidoreductase (POR) was significantly associated with severe TIPN (P value = 1.8 ×10-6). Six variants were predicted to be deleterious in POR. There were no associations between CYP2C8, CYP3A4, or CYP3A5 metabolizer status with severe TIPN.. Rare variants in POR predict an increased risk of severe TIPN in patients of European ancestry who receive paclitaxel.

Topics: Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP3A; Humans; Paclitaxel; Peripheral Nervous System Diseases; Quality of Life

Dose-limiting toxicities significantly impact the benefit/risk profile of many drugs. Whole genome sequencing (WGS) in patients receiving drugs with dose-limiting toxicities can identify therapeutic hypotheses to prevent these toxicities. Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting neurological toxicity of chemotherapies with no effective approach for prevention.. We conducted a genetic study of time-to-first peripheral neuropathy event using 30× germline WGS data from whole blood samples from 4900 European-ancestry cancer patients in 14 randomized controlled trials. A substantial number of patients in these trials received taxane and platinum-based chemotherapies as part of their treatment regimen, either standard of care or in combination with the PD-L1 inhibitor atezolizumab. The trials spanned several cancers including renal cell carcinoma, triple negative breast cancer, non-small cell lung cancer, small cell lung cancer, bladder cancer, ovarian cancer, and melanoma.. We identified a locus consisting of low-frequency variants in intron 13 of GRID2 associated with time-to-onset of first peripheral neuropathy (PN) indexed by rs17020773 (p = 2.03 × 10. Our genetic study provides insight into the impact of low-frequency and rare coding genetic variation on PN risk and suggests that further study of GPR68 in sensory neurons may yield a therapeutic hypothesis for prevention of CIPN.

Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Paclitaxel; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic; Receptors, G-Protein-Coupled; Taxoids

BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is most commonly associated with platinum-based drugs, taxanes, and vinca alkaloids. This prospective study from a single center in Kosovo aimed to evaluate CIPN in 120 patients receiving 4-6 cycles of platinum-based and taxane-based chemotherapy. MATERIAL AND METHODS One hundred twenty patients underwent neurological examination and nerve conduction studies (NCS) before chemotherapy, and after 4 to 6 cycles of treatment. Sixty patients were treated with platinum-based chemotherapy, 30 were treated with taxane-based chemotherapy, and 22 patients received a combination of platinum- and taxane-based chemotherapy. The most commonly used platinum-based compounds were oxaliplatin and carboplatin, whereas the most commonly used taxane medications were paclitaxel and docetaxel. Presence of neuropathy was confirmed with neurological examination of electrophysiological criteria applicable for polyneuropathies. Total Neuropathy Score (TNSr) was used to combine clinical and electrophysiological values. RESULTS Around 90% of patients self-reported neuropathic symptoms, and in 60% of them polyneuropathy was present in NCS. All sensory and motor nerves had significantly lower amplitudes (P<0.01). Platinum-based agents caused more pronounced decrease in ulnar nerve compound motor action potential (CMAP) (P<0.05); when used solely or in combination with taxanes, they caused significant decrease in tibial nerve CMAP (P<0.01). TNSr did not reach statistical significance between groups; only clinical muscle strength showed pronounced weakness in the combined protocol (P<0.05). CONCLUSIONS These findings support previous studies and show that CIPN, including sensory and motor symptoms, is commonly associated with chemotherapy. Platinum-based chemotherapy agents were more commonly associated with ulnar and tibial nerve damage in this study population.

Topics: Antineoplastic Agents; Bridged-Ring Compounds; Humans; Kosovo; Peripheral Nervous System Diseases; Platinum; Platinum Compounds; Prospective Studies; Taxoids

Topics: Antineoplastic Agents; Bridged-Ring Compounds; Humans; Peripheral Nervous System Diseases; Taxoids; Vitamin E

Topics: Bridged-Ring Compounds; Humans; Peripheral Nervous System Diseases; Taxoids; Vitamin E

Dramatic improvements in cancer survival have occurred in the last decade, but the quality of life for many survivors is compromised due to severe, long-lasting, and often irreversible side effects of chemotherapy. The neurological side effects, chemotherapy induced peripheral neuropathy (CIPN) and cancer related/induced cognitive impairment (CRCI/CICI), are under-recognized and can occur after chemotherapy, immunotherapy, or radiation. The cellular mechanisms underlying these neurological side effects are poorly understood and there are no effective treatments or preventions, other than reduction or termination of cancer therapy. In our preliminary prospective, non-interventional study to examine the side effects of chemotherapy in patients with breast cancer (NCT03872141), patients with breast cancer who received standard of care single agent weekly taxane-based chemotherapy were assessed at baseline, midpoint, and end of treatment for neurological and cognitive changes and for blood levels of potential protein biomarkers (n = 13). CIPN and CRCI both showed an increase in severity with accumulating taxane and these changes were compared to protein alternations over the course of treatment. Using peripheral blood collected from patients (n = 10) during chemotherapy and tested with an antibody array curated by the MD Anderson RPPA Core), we found that 19 proteins were increased, and 12 proteins decreased over 12 weeks of treatment. Among those downregulate were proteins known to be critical for neuronal viability and function including GRB2 (growth factor receptor-bound protein 2) and NCS1 (neuronal calcium sensor 1). Concurrently, proteins associated with apoptosis, including BAK1 (Bcl-1 homologous antagonist/killer), were upregulated. These results support the proposal that CIPN and CRCI increase with increasing taxane exposure, and identified several proteins that are altered with taxane exposure that could be implicated in their pathogenesis. In conclusion, our study provides evidence for progressive neurological changes and the rationale to investigate the molecular basis for these changes with the goal of target identification for mitigation of these neurological side effects.

Topics: Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Cognition; Female; Humans; Peripheral Nervous System Diseases; Prospective Studies; Quality of Life; Receptors, Growth Factor; Taxoids

Understanding the detailed symptom spectrum of chemotherapy-induced peripheral neuropathy (CIPN) could facilitate shared decision-making and promote early intervention.. To compare the symptom spectrum of patient-reported CIPN associated with nab-paclitaxel, paclitaxel, and docetaxel treatments among patients with breast cancer.. This prospective cohort study was conducted at 9 medical centers across China from 2019 to 2021. Participants included hospitalized women diagnosed with invasive breast cancer, assessed with overlap propensity score weighting. Data were analyzed from from December 2021 to May 2022.. Treatment with nab-paclitaxel-, paclitaxel-, or docetaxel-based regimens.. Patient-reported CIPN on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire: CIPN 20-item instruments, consisting of sensory, motor, and autonomic scales. Multiple regression models were adjusted for baseline patient, tumor, and treatment characteristics.. Of 1234 participants, the mean (SD) age was 50.9 (10.4) years, and 295 patients (23.9%) received nab-paclitaxel, 514 patients (41.7%) received paclitaxel, and 425 patients (34.4%) received docetaxel. The nab-paclitaxel group mostly reported numbness in hands or feet related to sensory symptoms (83 patients [81.4%]), while the paclitaxel and docetaxel groups reported mainly motor (eg, weakness in legs: 60 patients [47.2%] in the paclitaxel group; 52 patients [44.4%] in the docetaxel group) and autonomic (eg, blurred vision: 58 patients [45.7%] in the paclitaxel group; 51 patients [43.6%] in the docetaxel group) symptoms. Patients reported motor symptoms earlier than sensory abnormalities, with a median of 0.4 (95% CI, 0.4-2.3) weeks in the nab-paclitaxel group, 2.7 (95% CI, 1.7-3.4) weeks in the paclitaxel group, and 5.6 (95% CI, 3.1-6.1) weeks in the docetaxel group. After overlap propensity score weighting and compared with the nab-paclitaxel group, the risks of patient-reported CIPN were lower in the paclitaxel (hazard ratio [HR], 0.59 [95% CI, 0.41-0.87]; P = .008) and the docetaxel (HR, 0.65 [95% CI, 0.45-0.94]; P = .02) groups. Similarly, patients who received paclitaxel (HR, 0.44 [95% CI, 0.30-0.64]; P < .001) or docetaxel (HR, 0.52 [95% CI, 0.36-0.75]; P < .001) reported less sensory discomfort compared with those who received nab-paclitaxel. However, the risk of patients in the paclitaxel or docetaxel groups reporting motor (paclitaxel: HR, 0.76 [95% CI, 0.52-1.11]; P = .15; docetaxel: HR, 0.69 [95% CI, 0.47-1.01]; P = .05) and/or autonomic (paclitaxel: HR, 1.00 [95% CI, 0.68-1.49]; P = .98; docetaxel: HR, 0.88 [95% CI, 0.59-1.30]; P = .52) symptoms was not lower than that in the nab-paclitaxel group.. In this cohort study of women with invasive breast cancer, nab-paclitaxel was associated with more severe CIPN than either paclitaxel or docetaxel. In addition to sensory symptoms, the risk of motor and autonomic abnormalities was not low among these 3 taxanes, and patients-reported motor symptoms even earlier than sensory symptoms. These findings may facilitate early detection and intervention for CIPN in taxane treatments for breast cancer.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cohort Studies; Docetaxel; Female; Humans; Middle Aged; Paclitaxel; Patient Reported Outcome Measures; Peripheral Nervous System Diseases; Prospective Studies; Quality of Life; Taxoids

To identify genetic variants associated with chemotherapy-induced peripheral neuropathy (CIPN) symptoms among gynecologic cancer survivors and determine the variants' predictive power in addition to age and clinical factors at time of diagnosis.. Participants of a prospective cohort study on gynecologic cancers provided a DNA saliva sample and reported CIPN symptoms (FACT/GOG-Ntx). Genotyping of 23 single nucleotide polymorphisms (SNPs) previously identified as related to platinum- or taxane-induced neuropathy was performed using iPLEX Gold method. Risk allele carrier frequencies of 19 SNPs that passed quality checks were compared between those with/without high CIPN symptoms using logistic regression, adjusting for age. Receiver operating characteristic (ROC) curves using clinical risk factors (age, diabetes, BMI, Charlson Comorbidity Index, previous cancer diagnosis) with and without the identified SNPs were compared.. 107 individuals received platinum or taxane-based chemotherapy and provided sufficient DNA for analysis. Median age was 65.1 years; 39.6% had obesity and 8.4% diabetes; most had ovarian (58.9%) or uterine cancer (29.0%). Two SNPs were significantly associated with high CIPN symptomatology: rs3753753 in GPX7, OR = 2.55 (1.13, 5.72) and rs139887 in SOX10, 2.66 (1.18, 6.00). Including these two SNPs in a model with clinical characteristics led to an improved AUC for CIPN symptomatology (0.65 vs. 0.74, p = 0.04).. Genetic and clinical characteristics were predictive of higher CIPN symptomatology in gynecologic cancer survivors, and combining these factors resulted in superior predictive power compared with a model with clinical factors only. Prospective validation and assessment of clinical utility are warranted.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Cancer Survivors; Cohort Studies; Female; Genetic Predisposition to Disease; Genetic Variation; Genital Neoplasms, Female; Humans; Middle Aged; Organoplatinum Compounds; Peripheral Nervous System Diseases; Polymorphism, Single Nucleotide; Predictive Value of Tests; Prospective Studies; Taxoids

This study aimed to prospectively explore severity and prevalence of chemotherapy-induced peripheral neuropathy (CIPN) and examine the correlation between clinician-assessed (objective) and patient-reported (subjective) CIPN in breast cancer survivors receiving taxane.. This was a prospective, longitudinal study. Purposive sampling was adapted to enroll women newly diagnosed with breast cancer and about to receive taxane. The CIPN was assessed after breast cancer diagnosed and before chemotherapy (T1), before cycle 1 to 4 taxane infusion (T2 to T5), and after chemotherapy completion (T6 to T8). Total Neuropathy Score-clinical version (TNSc), Identification Pain Questionnaire (ID pain), Functional Assessment of Cancer Therapy-Taxane subscale (FACT-Tax), and Peripheral Neuropathy Scale (PNS) were utilized for measuring CIPN. Descriptive statistics, Pearson correlation coefficient, and generalized estimating equation were used to analyze data.. A total of 88 participants were included. Both clinician-assessed and patient-reported CIPN gradually increased between T1 and T6 and mildly decreased at T7 and T8. Fifty-five participants (62.5%) experienced CIPN at T8. Weak-to-moderate correlations between subjective and objective CIPN were found at T6 to T8 (r = 0.272-0.533, p < 0.05). The change of TNSc, FACT-Tax, and PNS were significant over time. However, the significant change of neuropathic pain was only found at T6.. The change of CIPN prevalence and severity were significant over time in survivors newly diagnosed with breast cancer. Specifically, the severest and highest CIPN was detected at chemotherapy completion. Survivors remained suffering from CIPN 3 months after chemotherapy completion. Besides, mild to moderate correlations between clinician-assessed and patient-reported CIPN were identified.

Topics: Adult; Aged; Breast Neoplasms; Bridged-Ring Compounds; Cancer Survivors; Female; Humans; Longitudinal Studies; Middle Aged; Peripheral Nervous System Diseases; Prospective Studies; Taxoids

Topics: Antineoplastic Agents; Bridged-Ring Compounds; Female; Humans; Peripheral Nervous System Diseases; Polymorphism, Genetic; Receptors, Lysophosphatidic Acid; Taxoids

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side-effect of neurotoxic cancer treatment impacting on long-term quality of life. Symptoms include numbness, tingling, and pain, affecting the distal extremities. However, patients often report symptoms discrepant from the expected symmetrical distribution and the degree of concurrence with objective assessment remains ill-defined. This study aimed to investigate severity and symmetry of neuropathy symptoms to enable comparison of objective measures and patient report.. Forty-five taxane-treated patients (F = 43, 66 ± 1.5 years, 19 months post-treatment) completed bilateral neuropathy assessments via clinical examination, sensory nerve conduction studies (NCS), and patient questionnaires. The laterality index (LI) was calculated as a ratio of smaller to larger side-to-side differences.. Neuropathy was reported by 89% of the cohort. On clinical examination, 83% had ≥ 2 abnormalities, with 38-35% having upper or lower limb sensory amplitudes below normative range. Thirty-five percent indicated side-to-side symptom asymmetry; however, there was no significant asymmetry evident on clinical examination (LI Asym = .60 ± .10, Sym = .76 ± .05, NS) and no difference in side-to-side NCS (median LI:Asym = .69 ± .06, Sym = .81 ± .04, NS; Sural LI:Asym = .80 ± .04, Sym = .81 ± .04, NS). Accordingly, there was no statistical association between patient-reported and objective assessment of side-to-side asymmetry, suggesting discordance between patient experience and objective assessment. Similarly, discrepancies in symptom severity between hands and feet were reported by 32% of the cohort. However, patients reporting differences in symptom severity between the hands and feet were just as likely to present with comparable assessments as to demonstrate objective discrepancies.. Discrepancies may exist between the patient experience of CIPN and objective assessments. Understanding these discrepancies may help to elucidate underlying mechanisms and better inform treatment strategies.

Topics: Adult; Aged; Antineoplastic Agents; Bridged-Ring Compounds; Female; Humans; Male; Middle Aged; Peripheral Nervous System Diseases; Taxoids

Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling complication related to taxanes. Underlying mechanisms are not completely understood and no specific treatment exists. We investigated the role of nerve conduction studies (NCS) and of serum osteopontin (OPN) measurement as a means to stratify the risk of developing taxane-induced neuropathy (TIN).. We enrolled 50 women with breast cancer treated with taxanes (docetaxel or paclitaxel) in a 3-month prospective study. They were evaluated before chemotherapy (time-point T0) and followed up at 1 (T1) and 3 (T2) months with clinical examinations/scales, quality of life (QoL) questionnaires, NCS, and serum OPN dosages.. A reduction of sural and superficial peroneal sensory action potentials was seen at T1, with a progression at T2 (P<0.001). In contrast, a significant impact of neuropathic symptoms on QoL only occurred at T2 (P<0.01). OPN levels at T0 inversely correlated to axonal loss in the sural nerve (T0-T2, P<0.01). OPN levels at T0 were lower in the intermediate and poor outcome patient subgroups, compared to the good outcome subgroup, as specifically defined (P<0.05).. Lower limb NCS changes occurred earlier than the detrimental effects of TIN on patients' QoL. Low serum OPN levels before chemotherapy may represent a novel biomarker of TIN risk.

Topics: Adult; Aged; Breast Neoplasms; Bridged-Ring Compounds; Female; Humans; Middle Aged; Neural Conduction; Osteopontin; Peripheral Nervous System Diseases; Prospective Studies; Taxoids

Taxanes are cornerstones of cancer chemotherapy and can be used for the treatment of various tumors, including breast cancer. Taxane-associated peripheral neuropathy is a common adverse effect of taxanes, leading to discontinuation of drug therapy, affecting drug treatment outcomes, and severely affecting patients' quality of life. This consensus addresses and recommends the pathogenesis, clinical features, associated risk factors, diagnostic evaluation, prevention, and treatment of taxane-related peripheral neuropathy. It is hoped that this consensus will standardize the current management of taxane-related peripheral neuropathy in China and improve clinicians' understanding of taxane-related peripheral neuropathy, thereby improving patient outcomes and improving patient quality of life.. 紫杉类药物是肿瘤化学治疗的基石药物，可用于包括乳腺癌在内的多种肿瘤的治疗。紫杉类药物相关周围神经病变是紫杉类药物的常见不良反应，可导致药物治疗中止，影响药物治疗结局，且严重影响患者的生活质量。《紫杉类药物相关周围神经病变规范化管理专家共识》针对紫杉类药物相关周围神经病变的发病机制、临床特点、相关危险因素、诊断评估、预防和治疗等展开阐述和推荐。希望本共识可规范当前国内紫杉类药物相关周围神经病变的管理，提高临床医师对紫杉类药物相关周围神经病变的认识，从而改善患者的治疗结局，提高患者生活质量。.

Topics: Antineoplastic Agents, Phytogenic; Breast Neoplasms; Bridged-Ring Compounds; China; Consensus; Humans; Neurotoxicity Syndromes; Peripheral Nervous System Diseases; Practice Guidelines as Topic; Quality of Life; Taxoids

To comprehensively describe patient-reported, functional and neurophysiological outcomes to elucidate the phenotypic profile of taxane-induced neuropathy.. Taxane-treated patients (n = 47) completed cross-sectional bilateral clinical and sensory assessments and nerve conduction studies. Patients reported symptom severity via Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx13) questionnaire.. Symptoms of neuropathy were reported by 81% of patients. On clinical examination, 62% had 2 or more abnormalities, with 20% indicating significant symptomatic and objective neuropathy. Nerve conduction studies were consistent with a sensory predominant axonal neuropathy. However, features more typical of entrapment neuropathy were also present in > 50%, which were not associated with overall severity of chemotherapy-induced peripheral neuropathy (CIPN) or clinical risk factors.. There is considerable variation in CIPN phenotypes associated with taxane-treatment. Understanding their clinical associations may assist in identification of patients at risk of severe neurotoxicity. This would enable treatment modification decisions but also limit early cessation of effective anti-cancer treatment in patients with less severe neurological sequelae.. Understanding the CIPN phenotype may inform treatment decisions which could impact clinical and survival outcomes.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Electrodiagnosis; Female; Humans; Middle Aged; Neurotoxicity Syndromes; Peripheral Nervous System Diseases; Phenotype; Taxoids; Urogenital Neoplasms

Breast cancer is the most common cancer among women. Localized breast cancer treatments involve taxanes which are often responsible for acute peripheral neuropathy. The persistence of taxane-induced peripheral neuropathy (TIPN) is scarcely described among elderly women. A monocenter historical cohort study including all women over 65 years of age treated between 2001 and 2016 with a taxane-based chemotherapy for localized breast cancer was carried out at the Paul Strauss Regional Comprehensive Cancer Center. All cases included were followed up for at least 2 years, deaths from causes unrelated to TIPN were excluded. We report on the frequency and risk factors and establish a prognostic score of persistent Common Terminology Criteria for Adverse Events (CTCAE) grade 2 and 3 TIPN. Among the 302 included patients, 21% and 9% developed persistent TIPN of grade 2 and 3, respectively. Two patients died from complications of grade 3 TIPN. Risk factors of persistent grade 2 and higher neuropathy included age (P < .0001), body mass index (P < .0001), and diabetes (P = .0093). Persistent TIPN was more frequent with paclitaxel than docetaxel (OR = 5.43; P < .0001). Patients presenting all four major risk factors had a 97.2% probability of developing long-term symptoms against 1.2% for patients showing no risk factor. We therefore identified 3 prognostic groups. TIPN is a frequent and sometimes severe persistent side effect of breast cancer treatment among elderly women with a major impact on health-related quality of life. Chemotherapy regimens without taxane could therefore be a valid option in elderly patients with neurotoxicity risk factors.

Topics: Aged; Breast Neoplasms; Bridged-Ring Compounds; Cohort Studies; Female; Humans; Paclitaxel; Peripheral Nervous System Diseases; Quality of Life; Taxoids

Treatment-induced peripheral neuropathy (TIPN) is a difficult problem experienced by patients with cancer that can interfere with their ability to receive optimal therapy. The Treatment-Induced Peripheral Neuropathy Scale (TNAS) is a patient-reported outcome (PRO) measure developed to assess TIPN symptom burden. However, PRO validation is an ongoing process. The aim of this qualitative study was to define the conceptual model, establish content domain validity, and refine items for the TNAS based on patient input.. Patients who received bortezomib, oxaliplatin, or platinum-taxane combination therapy reported their experience of TIPN in single qualitative audiotaped interviews. Themes of the TIPN experience were identified by descriptive analysis of the transcribed interviews.. Three groups of 10 patients each who had received bortezomib, oxaliplatin, or platinum-taxane combination therapy, for a total of 30 patients, reported their experiences. Two themes reported by patients were TIPN sensations and functional interference. Five sensations (numbness, tingling, pain, heat or burning, and coldness) and five functional impacts (using hands, walking, maintaining balance or falling, wearing shoes, and sleeping) were reported by at least 20% of patients and were selected for inclusion in the TNAS v3.0 for additional psychometric testing.. The assessment of TIPN must be convenient, reliable, and practical for patients, who are the most reliable source of information about symptoms. The TNAS, developed with direct patient input, provides an easily administered and conceptually valid method of patient report of TIPN burden for use in research and practice.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bortezomib; Bridged-Ring Compounds; Female; Humans; Male; Middle Aged; Neoplasms; Oxaliplatin; Patient Reported Outcome Measures; Peripheral Nervous System Diseases; Psychometrics; Taxoids

While older adults with cancer are more likely to develop chemotherapy-induced peripheral neuropathy (CIPN), the study aimed to determine if patient-reported and objective measures of CIPN differ by age among cancer survivors.. Cancer survivors with persistent CIPN after completion of platinum and/or taxane chemotherapy completed CIPN questionnaires (severity, interference with activities, sensory, and motor symptoms) and objective testing (light touch, vibration, pain, cold sensation). CIPN measures were compared by age group (< 65 n = 260 versus ≥ 65 n = 165) using parametric and nonparametric tests.. Among 425 cancer survivors with CIPN, mean age was 60.9 (SD 10.5). CIPN location did not differ by age (overall 68% hands and feet, 27% only feet, 5% only hands). For patient-reported measures, older survivors reported less severe pain in the hands and feet than younger survivors. In addition, older survivors reported lower interference with general activity, routine activities, normal work, enjoyment of life, sleep, mood, relations with other people, and sexual activity. No age differences in sensory and motor symptom scores were found. In contrast, for objective measures, older survivors had worse light touch and cold sensations in their feet and worse vibration detection in their hands and feet.. Despite having worse light touch, cold, and vibration sensations, older cancer survivors with CIPN reported less severe pain and interference with activities. This discordance highlights the importance of including both patient-reported and objective measures to assess CIPN in cancer survivors to better evaluate this clinical condition.

Topics: Aged; Antineoplastic Agents; Bridged-Ring Compounds; Cancer Survivors; Female; Humans; Induction Chemotherapy; Male; Middle Aged; Neoplasms; Pain; Patient Reported Outcome Measures; Peripheral Nervous System Diseases; Platinum; Self Report; Surveys and Questionnaires; Taxoids

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant and difficult to manage side effect of neurotoxic chemotherapies. Several risk factors for CIPN have been identified to date, but inconsistencies and methodological limitations exist in past research. Also, a limited number of potential risk factors has been investigated in the past.. The objective of this study was to assess the relative contribution of a wider range of risk factors in the development of CIPN.. This analysis used the 6-month data after starting chemotherapy from a larger prospective observational study on CIPN risk, prevalence, and quality of life. Patients were assessed at recruitment for possible CIPN risk factors, including prior history of neuropathies, current/past infectious diseases; neurotoxic medication history; personal and treatment characteristics; smoking history, alcohol use, and vegetable/fruit intake. Neuropathy was assessed at 6-months after starting chemotherapy with the neuropathy (motor/sensory) items of the NCI-CTCAE scale and the WHO criterion for neuropathy. Data on symptom burden were also collected.. Data were available from 255 patients from three cancer centers in Hong Kong, Singapore, and UK. The use of different scales did not always identify the same predictor variables. Key risk factors in multivariate regression models included older age (highest OR = 1.08, p < 0.01 with the WHO scale), chemotherapy (platinum-based chemotherapy had OR = 0.20-0.27 in developing CIPN compared to taxane-based chemotherapy), history of neuropathy (for motor CIPN only, OR = 8.36, p < 0.01), symptom burden (OR = 1.06, p < 0.05), number of chemotherapy cycles received (OR = 1.19-1.24, p < 0.01), and alcohol intake (OR = 0.32, p < 0.05). In univariate analysis, the use of statins was implicated with CIPN (p = 0.03-0.04 with different assessments) and diabetes showed a trend (p = 0.09) in the development of CIPN.. This study confirmed the CIPN risk related to certain variables and identified new ones. This knowledge can assist with treatment decisions and patient education.

Topics: Antineoplastic Agents; Bridged-Ring Compounds; Cancer Care Facilities; Cisplatin; Docetaxel; Female; Hong Kong; Humans; Male; Middle Aged; Neurotoxicity Syndromes; Peripheral Nervous System Diseases; Platinum Compounds; Prevalence; Prospective Studies; Quality of Life; Risk Factors; Taxoids

Topics: Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; G(M1) Ganglioside; Humans; Peripheral Nervous System Diseases; Taxoids

Medical practitioners have long associated the physical appearance of human fingernails with certain underlying health conditions due to their direct connection to the vascular system. The objective of this study was to demonstrate how human fingernails can potentially be used as a biomarker to determine the severity of a patient's reaction to chemotherapy.. Quantitative investigation of fingernails in patients undergoing taxane-based chemotherapy was conducted using a high-frequency 50 MHz ultrasound device in B-mode in the form of a pilot study. Time-of-Flight (TOF) ultrasonic signal measurements were recorded longitudinally across fingernails over three time intervals; (before treatment, in the middle of treatment, and on the last day of treatment); a neuropathy assessment and photographs were also taken for comparison.. A total of 17 patients were examined in this study with ages ranging from 35-69 years old with both weekly and biweekly chemotherapy regimens. Onycholysis and fingernail discoloration were observed in 8 of the 17 patients. White transverse lines and white lunula were observed on 4 of the 17 patients. Quantitative assessment revealed a TOF median decrease in fingernails during the first half of chemotherapy treatment; conversely, TOF median was found to have increased during the second half. Median TOF measurements at the end of treatment were found to return to approximately that of the baseline value.. This was a novel application of ultrasound in fingernails as chemotherapy biomarkers and further studies should be considered to verify and expand on the results obtained in this study.

Topics: Adult; Aged; Antineoplastic Agents; Bridged-Ring Compounds; Drug Monitoring; Female; Humans; Male; Middle Aged; Nails; Onycholysis; Peripheral Nervous System Diseases; Pigmentation Disorders; Pilot Projects; Taxoids; Ultrasonography

Topics: Animals; Antineoplastic Agents, Phytogenic; Bridged-Ring Compounds; Carcinoma, Non-Small-Cell Lung; Disease Models, Animal; Hyperalgesia; Lung Neoplasms; Male; Mice; Mice, Inbred C57BL; Nicotine; Paclitaxel; Peripheral Nervous System Diseases; Receptors, Cholinergic; Taxoids

Peripheral neuropathy is a common complication of cancer treatment impairing quality of life and function. This study explored the impact of a complementary and integrative medicine (CIM) program on taxane-induced peripheral neuropathy (TIPN).. Taxane-treated female patients with breast and gynecological cancer reporting TIPN-related symptoms were referred to an integrative physician, followed by patient-tailored CIM treatments (acupuncture with/without other modalities). Assessment of study outcomes at 6 to 12 weeks was conducted using the Measure Yourself Concerns and Wellbeing, which documented free-text narratives about patients' experience during the CIM treatment process. Content was analyzed using ATLAS.Ti software.. Of the 125 patients treated with taxanes, 69 had been referred for CIM treatment of TIPN-associated symptoms. Multidisciplinary narrative analysis identified 2 groups of CIM-treated patients: those with an apparently moderate improvement in symptoms (n = 35) and those with either only an apparent mild or no improvement at all. For 10 patients, assessment of their response to treatment was unclear. The 2 identified groups had similar demographic, cancer-related, and quality of life-related parameters at baseline. Content analysis of patients with an apparent moderate improvement suggested a short-term (24-48 hours) effect with acupuncture treatment, either alone or combined with manual, mind-body, and anthroposophic music therapies. Symptoms showing improvement included paresthesia and numbness.. Acupuncture and other CIM therapies may result in a short-term and transitory reduction in TIPN-related symptoms.

Topics: Aged; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Complementary Therapies; Female; Genital Neoplasms, Female; Humans; Integrative Medicine; Middle Aged; Peripheral Nervous System Diseases; Precision Medicine; Taxoids

The pathophysiology of chemotherapy-induced peripheral neuropathy (CIPN) is not well understood. Currently, dose reduction is the only recommendation for alleviating symptoms, often leading to premature treatment cessation. The primary aim of this analysis was to determine the association between components of diet during taxane treatment for breast cancer and change in CIPN symptoms over treatment.. Women with stage II or III invasive breast cancer were enrolled into an ancillary study to the North American Breast Cancer Intergroup phase III trial (S0221) led by the Southwest Oncology Group (SWOG). Questionnaires including a food frequency questionnaire and the Functional Assessment of Cancer Treatment Gynecologic Oncology Group-Neurotoxicity were administered to assess diet and neuropathic conditions at baseline and during chemotherapy. Ordinal regression was used to estimate odds ratios (ORs) for associations between various food groups and change in neuropathy score (< 10%, 10-30%, > 30%) (n = 900).. The odds of worse neuropathy decreased by 21% for each increase in tertile of grain consumption (OR = 0.79, 95% CI 0.66-0.94, p = 0.009). We also observed a nominal 19% increase with higher consumption of citrus fruits (OR = 1.19, 95% CI 1.01-1.40, p = 0.05).. Distinguishing between those who experienced a moderate and a severe change in neuropathy, we found that citrus fruit and grain consumption may play a role in the severity of symptoms. Since there are no existing dietary recommendations for the management of CIPN, further research is needed to investigate whether there may be certain foods that could worsen or alleviate neuropathy symptoms associated with treatment for breast cancer.. ClinicalTrials.gov, NCT03413761 . Registered retrospectively on 29 January 2018.

Topics: Adult; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Diet; Female; Humans; Middle Aged; Peripheral Nervous System Diseases; Quality of Life; Self Report; Taxoids

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of several commonly used chemotherapy drugs including taxanes, vinca alkaloids, and platinum compounds. Development of CIPN is highly variable, both in self-reported symptoms and functional consequences, and can be severe enough to alter dose intensity.. To describe the natural histories of both patient-reported symptoms of CIPN and functional impairments in breast cancer patients undergoing taxane-based chemotherapy.. Thirty-three breast cancer patients (32 female/1 male; 47.8 ± 11.2 years; n = 17 stage II/n = 16 stage III) were enrolled. Patients completed self-reports of symptoms and function (e.g., EORTC QLQ-CIPN20) and objective measures of physical function (i.e., balance and gait testing) in an outpatient oncology clinic at five timepoints: (1) baseline-prior to starting chemotherapy, (2-4) before starting subsequent chemotherapy cycles, and (5) 1-3 months after receiving their last taxane infusion.. Significant negative changes in both patient-reported outcomes and objective functional measures were observed. Decreased balance was observed after the first chemotherapy cycle (28% increase in medial-lateral excursion of the center of pressure, p = 0.016) and progressed with cumulative exposure (43% increase, p < 0.001). Patients also demonstrated slower walking speeds (5% decrease, p = 0.003) as they progressed through treatment. These functional deficits were mirrored with increased patient-reported symptom severity for all EORTC QLQ-CIPN20 subscales (all p < 0.05).. This study longitudinally assessed patient-reported outcomes concurrently with balance and gait testing in patients undergoing taxane therapy. Taxane treatment was associated with the development of clinically relevant problems in both CIPN symptoms and patient function.

Topics: Aged; Breast Neoplasms; Bridged-Ring Compounds; Female; Gait; Humans; Male; Middle Aged; Neoplasm Staging; Patient Reported Outcome Measures; Peripheral Nervous System Diseases; Postural Balance; Self Report; Taxoids; Treatment Outcome

The purpose of this study was to determine whether the presence of diabetes mellitus (DM) influences the incidence and severity of peripheral sensory neuropathy (PSN) in patients using taxane therapy.. A retrospective single-center analysis was conducted: Patients with PSN at baseline were excluded. The incidence of PSN was evaluated retrospectively in patient subgroups who received taxane arm and taxane-plus-platinum-agents combination arm with or without known DM at baseline.. Three hundred seventy-four patients were enrolled in this study, 81 (21.6%) of patients had DM at baseline. The incidence of grade 1 PSN (non-DM/DM) in patients receiving taxane-based chemotherapy was 33.4/25.9% and more than grade 2 PSN (non-DM/DM) was 15/34.6%. The rate of neuropathy of non-diabetic patients was 48.8%, while the rate of diabetic patients was 52.8 and 75% in DM duration below 5 years and above 5 years group, respectively.. This retrospective analysis indicates that taxane-based therapy in DM patients whose disease duration is above 5 years appears to affect the incidence and severity of PSN without known baseline neuropathy. The probability of PSN with taxane-based therapy was similar in DM duration below 5 years and non-DM patients.

Topics: Aged; Bridged-Ring Compounds; Diabetes Complications; Female; Humans; Incidence; Male; Neoplasms; Peripheral Nervous System Diseases; Retrospective Studies; Taxoids

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of neurotoxic chemotherapy resulting in pain, sensory loss, and decreased quality of life. Few studies have prospectively examined the relationship between sensory neuropathy symptoms, falls, and fall-related injuries for patients receiving neurotoxic chemotherapy.. To determine the association between the symptoms of CIPN and the risk of falls for patients receiving neurotoxic chemotherapy.. In this secondary analysis of a prospective study, 116 patients with breast, ovarian, or lung cancer who were beginning neurotoxic chemotherapy with a taxane or platinum agent were recruited from oncology clinics. These patients would call a novel automated telephone system daily for 1 full course of chemotherapy. The telephone system (SymptomCare@Home) used a series of relevant CIPN questions to track symptoms on a 0 to 10 ordinal scale and contained a questionnaire about falls. Those reporting a numbness and tingling severity score of 3 or greater for at least 10 days were considered to have significant CIPN symptoms and were compared with those patients who did not. Data analysis was performed in November 2015.. Chemotherapy with a neurotoxic taxane or platinum agent.. Patient-reported falls or near falls and fall-related injuries. The hypothesis was generated after data collection but prior to data analysis.. Of the 116 patients who started neurotoxic chemotherapy (mean [SD] age was 55.5 [11.9] years, and 109 [94.0%] were female), 32 met the predetermined criteria for CIPN symptoms. The mean duration of follow-up was 62 days, with 51 telephone calls completed per participant. Seventy-four falls or near falls were reported. The participants with CIPN symptoms were nearly 3 times more likely to report a fall or near fall than the participants without CIPN symptoms (hazard ratio, 2.67 [95% CI, 1.62-4.41]; P < .001). The participants with CIPN symptoms were more likely than the participants without CIPN symptoms to obtain medical care for falls (8 of 32 participants with CIPN symptoms [25.0%] vs 6 of 84 participants without CIPN symptoms [7.1%]; P = .01).. These findings suggest that the sensory symptoms of CIPN are an indicator of an increased risk of falling and an increased use of health care resources. This study demonstrates the utility of a novel telephone-based system to track neuropathy symptoms. Careful monitoring and coaching of patients receiving neurotoxic chemotherapy for new sensory symptoms may facilitate more effective fall prevention strategies.

Topics: Accidental Falls; Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Chi-Square Distribution; Female; Humans; Lung Neoplasms; Male; Middle Aged; Outcome Assessment, Health Care; Ovarian Neoplasms; Peripheral Nervous System Diseases; Platinum; Prospective Studies; Severity of Illness Index; Taxoids

To quantify the prevalence of neurological complications among breast cancer patients at one and three years after diagnosis, and to identify factors associated with neuropathic pain (NP) and chemotherapy-induced peripheral neuropathy (CIPN).. Prospective cohort study including 475 patients with newly diagnosed breast cancer, recruited among those proposed for surgical treatment (Portuguese Institute of Oncology, Porto). Patients underwent a neurological evaluation and had their cognitive function assesses with the Montreal Cognitive Assessment, before treatment and at one and three years after enrollment. We estimated the prevalence of each neurological complication, and odds ratios (OR), adjusted for socio-demographic and clinical characteristics, to identify factors associated with NP and CIPN.. More than half of the patients [54.7%, 95% confidence interval (95%CI): 50.2-59.2] presented at least one neurological complication, at one or at three years after cancer diagnosis. Between the first and the third year of follow-up, there was an increase in the prevalence of NP (from 21.1% to 23.6%), cognitive impairment (from 7.2% to 8.2%), cerebrovascular disease (from 0.6% to 1.5%) and brain metastasis (from 0.0% to 0.6%). The prevalence of CIPN decreased from 14.1% to 12.6%. Axillary lymph node dissection was associated with NP at one year (OR = 2.75, 95%CI: 1.34-5.63) and chemotherapy with NP at three years (OR = 2.10, 95%CI: 1.20-3.67). Taxane-based chemotherapy was strongly associated with prevalence of CIPN at one and three years.. Neurological complications are frequent even three years after cancer diagnosis and NP remained the major contributor to the burden of these conditions among survivors.

Topics: Adult; Antineoplastic Agents; Axilla; Brain Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Intraductal, Noninfiltrating; Cerebrovascular Disorders; Cognitive Dysfunction; Female; Follow-Up Studies; Humans; Lymph Node Excision; Middle Aged; Neuralgia; Neurotoxicity Syndromes; Peripheral Nervous System Diseases; Prevalence; Prospective Studies; Risk Factors; Survivors; Taxoids

Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity secondary to chemotherapy. Genetic factors may be important in predisposing patients to this adverse effect.. We studied 950 primary lung cancer patients, who received platinum or platinum-combination drug chemotherapy and who had DNA available for study. We analyzed epidemiological risk factors in 279 CIPN patients and 456 non-CIPN patients and genetic risk factors in 141 CIPN patients and 259 non-CIPN patients. The risk factors studied included demographic, diagnostic, and treatment data, as well as 174 tag SNPs (single nucleotide polymorphisms) across 43 candidate genes in the glutathione, cell cycle, DNA repair, cell signaling, and apoptosis pathways.. Patients who had diabetes mellitus were more likely to have CIPN (p=0.0002). Other epidemiologic risk factors associated with CIPN included number of cycles (p=0.0004) and type of concurrent chemotherapy (p<0.001). SNPs most associated with CIPN were in glutathione peroxidase 7 (GPX7) gene (p values 0.0015 and 0.0028, unadjusted and adjusted) and in ATP-binding cassette sub-family C member 4 (ABCC4) gene (p values 0.037 and 0.006, unadjusted and adjusted). We also found other suggestive associations in methyl-o-guanine-methyl-transferase (MGMT) and glutathione-S-transferase (GST) isoforms.. Epidemiological and genetic risk factors associated with CIPN in this cohort, included the type of chemotherapy drug, intensity of chemotherapy treatment, and genes known to be associated with chemotherapy resistance. These findings suggest that differentiating between cytotoxic and neurotoxic mechanisms of chemotherapy drugs is challenging but represents an important step toward individualized therapy and improving quality of life for patients.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Cohort Studies; DNA Modification Methylases; DNA Repair Enzymes; Female; Glutathione Peroxidase; Humans; Lung Neoplasms; Male; Middle Aged; Multidrug Resistance-Associated Proteins; Organic Anion Transporters; Peripheral Nervous System Diseases; Peroxidases; Platinum; Polymorphism, Single Nucleotide; Risk Factors; Taxoids; Tumor Suppressor Proteins

Taxane-induced peripheral neuropathy (TIPN) is an important survivorship issue for many cancer patients. Currently, there are no clinically implemented biomarkers to predict which patients might be at increased risk for TIPN. We present a comprehensive approach to identification of genetic variants to predict TIPN.. We performed a genome-wide association study (GWAS) in 3,431 patients from the phase III adjuvant breast cancer trial, ECOG-5103 to compare genotypes with TIPN. We performed candidate validation of top SNPs for TIPN in another phase III adjuvant breast cancer trial, ECOG-1199.. When evaluating for grade 3-4 TIPN, 120 SNPs had a P value of <10(-4) from patients of European descent (EA) in ECOG-5103. Thirty candidate SNPs were subsequently tested in ECOG-1199 and SNP rs3125923 was found to be significantly associated with grade 3-4 TIPN (P = 1.7 × 10(-3); OR, 1.8). Race was also a major predictor of TIPN, with patients of African descent (AA) experiencing increased risk of grade 2-4 TIPN (HR, 2.1; P = 5.6 × 10(-16)) and grade 3-4 TIPN (HR, 2.6; P = 1.1 × 10(-11)) compared with others. An SNP in FCAMR, rs1856746, had a trend toward an association with grade 2-4 TIPN in AA patients from the GWAS in ECOG-5103 (OR, 5.5; P = 1.6 × 10(-7)).. rs3125923 represents a validated SNP to predict grade 3-4 TIPN. Genetically determined AA race represents the most significant predictor of TIPN.

Topics: Black People; Breast Neoplasms; Bridged-Ring Compounds; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Peripheral Nervous System Diseases; Polymorphism, Single Nucleotide; Receptors, Fc; Taxoids; White People

Major advances in early detection and therapy have significantly increased the survival of breast cancer patients. Unfortunately, most cancer therapies are known to carry a substantial risk of adverse long-term treatment-related effects. Little is known about patient susceptibility to severe side effects after chemotherapy. Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of taxanes. Recent advances in genome-wide genotyping and sequencing technologies have supported the discoveries of a number of pharmacogenetic markers that predict response to chemotherapy. However, effectively implementing these pharmacogenetic markers in the clinic remains a major challenge. On the other hand, recent advances in proteomic technologies incorporating mass spectrometry (MS) for biomarker discovery show great promise to provide clinically relevant protein biomarkers. In this study, we evaluated the association between protein content in serum exosomes and severity of CIPN. Women with early stage breast cancer receiving adjuvant taxane chemotherapy were assessed with the FACT-Ntx score and serum was collected before and after the taxane treatment. Based on the change in FACT-Ntx score from baseline to 12 month follow-up, we separated patients into two groups: those who had no change (Group 1, N = 9) and those who had a ≥20% worsening (Group 1, N = 8). MS-based proteomics technology was used to identify proteins present in serum exosomes to determine potential biomarkers. Mann-Whitney-Wilcoxon analysis was applied and maximum FDR was controlled at 20%. From the serum exosomes derived from this cohort, we identified over 700 proteins known to be in different subcellular locations and have different functions. Statistical analysis revealed a 12-protein signature that resulted in a distinct separation between baseline serum samples of both groups (q<0.2) suggesting that the baseline samples can predict subsequent neurotoxicity. These toxicity-associated biomarkers can be further validated in larger retrospective cohorts for their utility in identifying patients at high risk for CIPN.

Topics: Adult; Antineoplastic Agents; Biomarkers, Tumor; Breast Neoplasms; Bridged-Ring Compounds; Case-Control Studies; Chemotherapy, Adjuvant; Cohort Studies; Exosomes; Female; Humans; Middle Aged; Neoplasm Proteins; Peripheral Nervous System Diseases; Prospective Studies; Proteomics; Risk Factors; Tandem Mass Spectrometry; Taxoids

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.. 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.. The AML test provided strong evidence for the association of some SNPs with TRSN (P = 0.023). The two most significantly associated SNPs were rs3213619(ABCB1) [OR = 0.47; 95% confidence interval (CI), 0.28-0.79; P = 0.004] and rs9501929(TUBB2A) (OR = 1.80; 95% CI, 1.20-2.72; P = 0.005). A further 9 SNPs were significant at P-value ≤ 0.05.. 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.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Female; Genome-Wide Association Study; Humans; Middle Aged; Neoplasm Staging; Odds Ratio; Paclitaxel; Peripheral Nervous System Diseases; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Taxoids

Clinical outcomes, including adverse events, in 52 advanced breast cancer patients treated with eribulin chemotherapy after taxane treatment (TX) were analyzed to confirm the effectiveness and safety of this treatment.The objective response rate (ORR) in patients was 34.6% (TX group 31.6%, non-TX group 36.4%). There were no significant differences in overall survival, time to treatment failure, or progression-free between three TX and non-TX groups. Further, adverse events did not differ between groups expression of neutropenia of Grade 3 or more. On the other hand, the number of patients with sensory peripheral neuropathy of Grade 1 or more was significantly more in the TX group than in the non-TX group. Eribulin chemotherapy was effective for the treatment of advanced breast cancer regardless of a history of taxane treatment.In addition, sensory peripheral neuropathy is a possible complication that can occur in advanced breast cancer patients treated with eribulin chemotherapy with taxane treatment history.

Topics: Breast Neoplasms; Bridged-Ring Compounds; Drug Resistance, Neoplasm; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Peripheral Nervous System Diseases; Taxoids