Patient Neurotoxicity Questionnaire Research Articles

Effect of frozen gloves on chemotherapy-induced neurotoxicity in breast cancer patients: a systematic review and meta-analysis.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a dose-limiting side effect observed in breast cancer patients. Its primary clinical manifestations include limb numbness, tingling sensations, hypoesthesia, or paresthesia. In severe instances, some patients may also encounter muscle cramps, weakness, and pain, leading to potential paralysis. The onset of CIPN significantly impacts the quality of life for cancer patients. Hence, it is imperative to explore preventive strategies for managing CIPN. We searched for relevant randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs) in several databases. The primary outcome measures encompassed the Patient Neurotoxicity Questionnaire (PNQ), the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane), and the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Secondary outcomes aimed to evaluate the quality of life and the tolerability of ice gloves. Meta-analysis was conducted using RevMan 5.3 software to determine the relative risk ratio (RR) and 95% confidence interval (CI). We conducted an analysis involving 372 patients across seven trials. In our meta-analysis, the use of ice gloves demonstrated non-significant results in reducing the incidence of both motor and sensory neuropathy, as assessed through CTCAE (sensory: RR: 0.94; 95% CI: 0.85 to 1.02; P = 0.15; motor: RR: 1.04; 95% CI: 0.88 to 1.22; P = 0.64). Similarly, when evaluated using the PNQ, there was no significant reduction observed in the incidence of sensory and motor neuropathy (sensory: RR: 0.49; 95% CI: 0.20 to 1.20; P = 0.12; motor: RR: 0.71; 95% CI: 0.26 to 1.99; P = 0.52). Consistently, our conclusions remained unchanged when employing the FACT-Taxane assessment. Regarding the evaluation of the quality of life, our observations suggested a potential improvement with the use of ice gloves, and participants exhibited moderate tolerance towards them. Ice gloves are a reasonable option for the treatment of CIPN in patients undergoing chemotherapy for breast cancer. However, the effectiveness of ice gloves in combating CIPN remains inconclusive at this time due to the low quality and limited number of clinical trials on this topic. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023457045, identifier CRD42023457045.

Safety and Efficacy of Compression Therapy to Prevent Chemotherapy-Induced Peripheral Neuropathy in Lower Extremities of Breast Cancer Patients: A Pilot Study.

Background Chemotherapy-induced peripheral neuropathy (CIPN) is a problematic adverse event for breast cancer patients receiving taxane antimitotic agents. We evaluated the effectiveness of compression therapy against CIPN in the lower extremities of breast cancer patients receiving taxanes. Methods Eligible patients scheduled for perioperative treatment with taxanes for early-stage breast cancer were enrolled. Each patient wore latex-free surgical gloves and compression socks, putting on two layers of each 15 minutes before the administration of taxanes and removing them 15 minutes after administration. Peripheral neuropathy (PN) was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and the Patient Neurotoxicity Questionnaire (PNQ). The primary endpoint was the incidence of CTCAE version 4.0 grade 2 or higher CIPN in the lower extremities during the entire period of perioperative chemotherapy with taxanes. Results PN assessment by CTCAE in the lower extremities, the primary outcome, showed that 13.3% developed grade 2 sensory disturbances, and 8.3% developed grade 2 motor disturbances. The incidence of CTCAE grade 2 or higher PN in the hands was 26.7% for sensory disturbances and 13.3% for motor disturbances during the entire study period. No patient had grade 3 or higher PN. No adverse events due to compression therapy were observed. Conclusion Compression of the lower extremities with compression socks tended to reduce the incidence of CIPN compared to the general incidence. Compression therapy may help prevent the development of CIPN.

Effects of taxane-induced peripheral neuropathy on hand dexterity impairment: evaluation of quantitative and subjective assessments.

Chemotherapy-induced peripheral neuropathy (CIPN) commonly involves hand dexterity impairment. However, the factors affecting hand dexterity impairment are unknown and there is currently no established treatment. The purpose of the current study was to clarify factors influencing hand dexterity impairment in taxane-induced peripheral neuropathy using subjective and objective assessments. We assessed patient characteristics, treatment-related factors, subjective symptoms of CIPN (Patient Neurotoxicity Questionnaire [PNQ]), psychological symptoms, and upper limb dysfunction (Quick Disabilities of the Arm, Shoulder and Hand [Quick DASH]). Quantitative assessments were pinch strength, sensory threshold, hand dexterity impairment, and grip force control. Multiple regression analysis was performed using hand dexterity impairment as the dependent variable and age and PNQ, Quick DASH, and control of grip force as independent variables. Forty-three breast cancer patients were included in the analysis. Hand dexterity impairment in taxane-induced peripheral neuropathy patients was significantly correlated with age, grip force control, and PNQ sensory scores (p < 0.008). Multiple regression analysis demonstrated that PNQ sensory scores and grip force control were significantly associated with hand dexterity impairment (p < 0.01). Subjective symptoms (numbness and pain) and grip force control contributed to impaired hand dexterity in taxane-induced peripheral neuropathy.

A randomized trial to evaluate the preventive effect of lafutidine on chemotherapy-induced peripheral neuropathy in patients treated with carboplatin and paclitaxel for lung cancer.

Chemotherapy-induced peripheral neuropathy (CIPN) has a significant impact on the therapeutic efficacy of chemotherapy and patients' quality of life. The aim of this study was to assess the preventive effect of lafutidine on CIPN. Patients were randomly assigned (1:1) to carboplatin and paclitaxel chemotherapy with lafutidine 10 mg twice daily (lafutidine group) or without lafutidine (control group). Peripheral neuropathy in both groups was assessed with the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and two patient-based questionnaires, the Patient Neurotoxicity Questionnaire (PNQ) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx). The primary outcome was the incidence of grade 2 or higher peripheral neuropathy in CTCAE version 5.0. The target number of cases was set at approximately 40. In total, 18 patients were screened, and 16 patients were assigned to the lafutidine group (n=9) or control group (n=7) between January 2021 and January 2023. Due to poor recruitment, the target number of cases was not reached. Grade 2 or higher neuralgia was 22.2% in the lafutidine group and 14.3% in the control group. Grade 2 or higher peripheral sensory neuropathy was 100% in the lafutidine group and 71.4% in the control group (P=0.175). Grade 3 or higher peripheral neuropathy was not detected in either group. There was no significant difference in PNQ scores between the two groups. Median FACT/GOGNtx scores after the fourth cycle tended to be lower in the lafutidine group than in the control group. There was no statistically significant difference in progression free survival (PFS) between the two groups. There were no adverse events due to lafutidine administration. Although the preventive effect of lafutidine on CIPN could not be demonstrated statistically, lafutidine FACT/GOG-Ntx scores showed a trend toward decreased neurotoxicity as chemotherapy proceeded. More reliable studies using lafutidine on the prevention of CIPN should be conducted. Japan Registry of Clinical Trials identifier: jRCTs021200031.

Cryocompression to Reduce Peripheral Neuropathy in Gynecologic Cancer: A Randomized Controlled Trial.

To investigate the efficacy of cryocompression therapy to prevent chemotherapy-induced peripheral neuropathy. This single-institution, randomized, self-controlled trial of cryocompression enrolled gynecologic cancer patients planned for five to six cycles neurotoxic chemotherapy. Exclusion criteria were prior neurotoxic chemotherapy or baseline peripheral neuropathy. Participants were randomized to cryocompression on dominant versus non-dominant hand and foot (treatment), with no intervention on the opposite side (control). Compression socks and gloves and ice bags were applied 15 minutes before, during, and 15 minutes after infusion. Primary outcome measures included the PNQ (Patient Neurotoxicity Questionnaire) and the Semmes-Weinstein monofilament test; secondary outcomes included the FACT/GOG-NTX (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity) and patient acceptability and tolerability. Sixty patients completing the study were necessary to detect a 70% reduction in the odds of PNQ grade C or higher peripheral sensory neuropathy with 80% power. Ninety-one patients were enrolled from January 2021 to October 2022; 69 were eligible for final analysis. Of the 91 patients, 64.8% were White, 30.8% were Black, and 1.1% were Hispanic or Latina. With successive cycles, more patients had sensory PNQ grade C or higher neuropathy on the control side compared with the cryocompression side. Cryocompression decreased the odds of sensory neuropathy (PNQ grade C or higher) by 46% at final visit (odds ratio 0.54, 95% CI 0.31-0.94; P =.03). There was no difference in tactile sensitivity based on the monofilament test between sides at the final visit. At the final visit, average FACT/GOG-NTX-11 (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity 11 Item Version) scores were significantly lower on the cryocompression than the control side (estimate -0.97, 95% CI -1.89 to -0.06; P =.04), as were FACT/GOG-NTX-4 (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity 4 Item Version) scores (estimate -0.35, 95% CI -0.64 to -0.05; P =.02). More than 85% of patients assessed the intervention as acceptable and tolerable. Cryocompression therapy reduces subjective chemotherapy-induced peripheral sensory neuropathy in patients who are receiving paclitaxel or cisplatin for gynecologic cancer. ClinicalTrials.gov , NCT04563130.

A meta-analysis studying the utility of cryotherapy in the prevention of peripheral neuropathy in breast cancer patients receiving paclitaxel and nab-paclitaxel.

12025 Background: Debilitating Peripheral Neuropathy (PN) caused by paclitaxel adversely impacts the quality of life in Breast Cancer (BC) patients. Cryotherapy using cooling devices during taxane infusion is a non-invasive strategy to prevent PN, but its efficacy has not been established. We hope to answer this question through our meta-analysis. Methods: A systematic search with keywords and controlled vocabulary encompassing BC, antineoplastics, and paclitaxel was conducted in PubMed, CINHAL, Embase, Scopus, Web of Science Collections, and CENTRAL. All databases were searched on March 7, 2022. There were no search restrictions on date, language, status, or outcomes. 405 records were identified, and duplicates were removed using EndNote 20. The remaining 372 records were imported into Covidence, and the titles and abstracts were screened independently by 2 reviewers. 22 out of 63 full texts were relevant to our question of which 14 [12 Randomized control studies and 2 retrospective studies] were included for the meta-analysis using R package meta. Only studies that analyzed cryotherapy use in BC patients who received paclitaxel or nab-paclitaxel were included. Relative risk (RR) derived from random effects model with Mantel-Haenszel method was used to compare the occurrence of PN between cryotherapy vs placebo groups. Results: Pooled incidence of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 PN was 24.85% (81/326) in the cryotherapy arm and 42.35% (72/170) in the placebo arm. Overall RR for CTCAE grade ≥ 2 PN with cryotherapy compared to placebo was 0.45 [0.27,0.77, p = 0.0031]. RR for sensory PN was 0.19 [0.05,0.66, p = 0.009] and for motor PN was 0.18 [0.03,0.99, p = 0.0491]. RR for Patient Neurotoxicity Questionnaire (PNQ) score ≥ D which connotes severe neuropathy was 0.24 [0.09,0.62, p = 0.0035]. Cold intolerance was the predominant adverse effect at 15% (37/247). Fingernail paronychia and skin irritation were reported at 0.8% (2/247) each. 5.1% (15/294) stopped cryotherapy use prior to completion. However, this number was driven by a single study (10/16 patients stopped using cryotherapy due to cold intolerance) and 7/11 studies had no discontinuations. Visual inspection of our funnel plots revealed no publication bias. Conclusions: Use of cryotherapy decreased the occurrence of CTCAE grade ≥ 2 PN by 55% in BC patients getting paclitaxel or nab-paclitaxel. Occurrence of both sensory and motor PN were lower. Cold intolerance was the most frequently reported issue with its use but lead to relatively low discontinuation rates in most studies. Given the lack of any severe adverse effect, cryotherapy use must be encouraged for patients receiving paclitaxel and nab-paclitaxel. Further studies are needed establish a standardized way of applying cryotherapy in terms of the device to use, timing and other logistical factors.

Patient-reported motor chemotherapy-induced peripheral neuropathy impacts function in advanced colorectal cancer survivors receiving chemotherapy: A cross-sectional study.

Chemotherapy-induced peripheral neuropathy limits cancer survivors' compliance with chemotherapy and impaired function. This study aimed to examine separate impacts of clinician-assessed, patient-reported sensory and motor chemotherapy-induced peripheral neuropathy on physical/role function and functional interference in advanced colorectal cancer survivors receiving chemotherapy. A cross-sectional, correlational design utilizing convenience sampling enrolled 75 stage III or IV colorectal cancer adults undergoing chemotherapy. Participants filled out the Patient Neurotoxicity Questionnaire, Identification Pain Questionnaire, and Peripheral Neuropathy Scale. Then, a trained research nurse conducted a brief neurological assessment using the Total Neuropathy Scale - clinical version. The prevalence of sensory and motor chemotherapy-induced peripheral neuropathy was from 34.7% to 54.7% and from 16.0% to 17.3%, respectively. Further, 20% of participants suffered from neuropathic pain. A low correlation between clinician-assessed and patient-reported chemotherapy-induced peripheral neuropathy was detected. The function was significantly impacted by patient-reported motor chemotherapy-induced peripheral neuropathy. This study was superior in utilizing the brief and valid patient-reported and clinician-assessed tools to measure sensory and motor chemotherapy-induced peripheral neuropathy. Moreover, the identification of patient-reported motor symptoms has the largest influence on function in advanced colorectal cancer survivors. Nurses may use the brief and easily administered tools in clinical settings for effective screening and early detection of motor and sensory chemotherapy-induced peripheral neuropathy to prevent functional decline in advanced colorectal cancer survivors. However, this study was still limited because of the cross-sectional design, small sample size, sample heterogeneity, and recruiting participants from only one medical center.

Mitigation of paclitaxel-induced peripheral neuropathy in breast cancer patients using limb-cooling apparatus: a study protocol for a randomized controlled trial.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common adverse events that can significantly impair the quality of life of patients. Although limb cooling may be beneficial for preventing CIPN, logistical challenges exist in ensuring consistent efficacy and safety. The purpose of this randomized controlled trial is to validate whether limb cooling with strict temperature control can reduce CIPN in patients with breast cancer receiving weekly paclitaxel as a perioperative treatment. This study is a multicenter, double-blinded, randomized controlled trial. We plan to enroll patients with breast cancer who are scheduled to receive 12 weekly doses of paclitaxel (60 min 80 mg/m2 intravenous infusion) as perioperative chemotherapy. Patients will be randomly divided into the intervention or control groups and undergo limb cooling therapy maintained at a constant temperature of 13°C and 25°C, respectively. The primary endpoint is the proportion of patients who report Patient Neurotoxicity Questionnaire (PNQ) ≥ D in their limbs by the end of the study treatment or at the time of discontinuation. The results of this trial will contribute to the establishment of new evidence for limb cooling therapy in the mitigation of CIPN and present a safe and stable cooling device that may be suitable for use in the clinic. https://jrct.niph.go.jp/en-latest-detail/jRCT2032210115, identifier jRCT2032210115.

A Randomized Controlled Phase 2 Study of Neoadjuvant Eribulin Versus Paclitaxel in Women with Operable Breast Cancer: The JONIE-3 Study

ObjectiveNeoadjuvant chemotherapy (NAC) is essential for surgical downstaging of early-stage breast cancer, but taxane administration is associated with neuropathy. We investigated whether eribulin induces less neuropathy than paclitaxel. MethodsIn this multicentre, randomised study (UMIN000012817), patients diagnosed with invasive breast cancer between December 2013 and April 2016 were randomly assigned to group E (eribulin followed by fluorouracil, epirubicin, and cyclophosphamide; FEC) or group P (paclitaxel followed by FEC). The primary endpoint was incidence of grade 1 or higher peripheral neuropathy according to the Common Terminology Criteria for Adverse Events (CTCAE). Secondary endpoints were pathological complete response (pCR), clinical response, breast-conserving surgery, adverse events, disease-free survival (DFS), and patient neurotoxicity questionnaire (PNQ) analysis. ResultsOne hundred and eighteen cases were analyzed for safety and 115 were evaluated for efficacy. Peripheral sensory neuropathy was significantly lower in group E after week 6, while peripheral motor neuropathy in group E was significantly lower at weeks 9, 12, and 15. pCR in groups E and P was 20.7% and 29.8% (P = .289), respectively, and clinical response was 55.2% and 77.2% (P = .017), respectively. Three-year DFS was 89.7% in group E and 86.0% in group P (P = .561). Neutropenia was more frequent and more severe in group E. PNQ was evaluated for 4 years, and item 1 (sensory) was consistently lower in group E. ConclusionNeuropathy was significantly less frequent and less severe in patients who received eribulin compared with paclitaxel. Thus, eribulin could be a good alternative to paclitaxel in patients suffering severe neuropathy.

QoL analysis: A randomized phase 3 study of sequential versus combination treatment in first-line chemotherapy for metastatic colorectal cancer—The C-cubed study.

102 Background: The C-cubed (C3) study demonstrated a sequential approach start from fluoropyrimidines (FP) plus bevacizumab (Bmab) followed by oxaliplatin (OX) adding significantly improved a median Treatment failure of strategy (TFS) for a combination approach start from FP+OX+Bmab [15.2 months vs. 7.6 months, HR, 0.475; 95% CI, 0.362 to 0.623; p &lt; 0.0001] in first-line metastatic colorectal cancer (mCRC). In this congress, we focus on the quality of life (QOL) assessments as a pre-planned analysis. (Study information: UMIN000015405). Methods: The C3 study was a randomized phase III study which evaluated the time to discontinuation of OX-containing therapy (sequential approach [Capecitabine/5-FU (FP)+Bmab followed by OX-FP+Bmab] vs. combination approach [OX-FP+Bmab]. The primary endpoint was TFS and secondary endpoints were ORR, OS, PFS, Safety and QoL. QOL assessments included European Organisation for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire for cancer (QLQ-C30) (EORTC QLQ C-30), EuroQol 5D 5L (EQ5D) and the Patient Neurotoxicity Questionnaire (PNQ) in both arm as a pre-planned analysis. Each questionnaire was collected at the time of enrolment, 6, 12, 18 months and end of treatment. QOL scores were compared using a mixed-effects models for repeated measures (MMRM). Results: A total 292 patients participated in QoL part (arm A: n =148; arm B: n =144). The returned questionnaire sheets were 292 (reply rate: 97%), 206 (68%), 199 (65%), 61 (20%) at baseline, 6, 12, 18 months, respectively. Sequential approach was statistically improved than combination approach as follows: Physical functioning (p&lt;0.001), Cognitive functioning (p=0.012), Social functioning (p=0.0004), and Fatigue (p=0.013) in EORTC QLQ C-30. In addition, at 6 months (after which attrition in the combination arm was more than 50%) after randomization, the mean change rate from baseline of EQ5D score in the sequential approach versus combination approach were: –1.91 (SD 27.57) versus –9.62 (29.60). In contract, PNQ sensory score showed that sequential approach was not statistically improved for combination approach (0.22 [SD: 0.89] vs. 0.61 [SD: 0.95], p=0.115). Conclusions: The further clarification of patients’ characteristics are needed, but this sequential approach can be advocated as a valuable treatment option in first-line mCRC for current guideline based on these QoLs and main efficacy data.

Проспективная комплексная оценка химиоиндуцированной периферической нейропатии у пациенток с раком молочной железы

Introduction. Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-dependent side effect of anticancer therapy that affects the patient’s quality of life. Currently, the problem of effective and reliable diagnostics for CIPN remains unresolved. Therefore, it is critically important to develop recommendations for a comprehensive assessment of peripheral neuropathy based on simple tests for vibration, tactile, pain sensitivity together with questionnaires. Aim. A prospective comprehensive assessment of the incidence and severity of CIPN using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) and the Patient Neurotoxicity Questionnaire (PNQ) in patients with breast cancer treated with taxanes. Materials and methods. Symptoms of CIPN were prospectively assessed in 60 patients using the PNQ, the NCI-CTCAE and the Eastern Cooperative Oncology Group (ECOG) Performance Status scores at baseline, 1 week after and 13 weeks after the start of chemotherapy. Results. The CIPN scores according to the PNQ were widely distributed among patients compared to the NCI-CTCAE scores for both sensory and motor neuropathy. There was a marked increase in symptoms of motor neuropathy in patients who were identified only on the basis of PNQ data. The PNQ was used to formally assess the impact of neuropathy on the patient’s activities of daily living. Conclusion. A comprehensive methodology based on a neurological examination together with the NCI-CTCAE and the PNQ will allow a more detailed assessment of the severity of СIPN, and in the future will provide an opportunity to develop a more effective patient management plan. The PNQ has shown itself to be a more sensitive tool compared to the NCI-STCAE, especially in assessing sensory neuropathy. Thus, it is reasonable to include patient-reported data in the evaluation of СIPN in order to provide a more accurate identification of the frequency and severity of neuropathy.

Health-Related Quality of Life With Trastuzumab Monotherapy Versus Trastuzumab Plus Standard Chemotherapy as Adjuvant Therapy in Older Patients With HER2-Positive Breast Cancer.

We report findings on quality of life (QoL) in the RESPECT trial, which compared adjuvant trastuzumab monotherapy with trastuzumab plus chemotherapy in older patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). Patients age 70-80 years with human epidermal growth factor receptor 2-positive surgically treated breast cancer were randomly assigned to receive trastuzumab (T) or trastuzumab plus chemotherapy (T + C). QoL was assessed using the Functional Assessment of Cancer Therapy-General (FACT-G), Philadelphia Geriatric Center Morale Scale, Hospital Anxiety and Depression Scale, Patient Neurotoxicity Questionnaire, and Tokyo Metropolitan Institute of Gerontology Index of Competence at baseline and after 2, 12, and 36 months. Comparisons were based on individual changes from baseline and were performed by Fisher's test or mixed-model repeated-measures. Among 275 patients in the parent study, 231 (84%) (average age: 74 years) were included in the analysis. At 2, 12, and 36 months, 198, 177, and 178 patients completed surveys, and the mean FACT-G scores at each survey point were 78.9, 80.4, 82.7, and 79.1 in group T and 79.5, 74.5, 78.4, and 78.5 in group T + C. Compared with group T + C, the proportion of patients showing QoL deterioration (≥ 5 points decrease from baseline in FACT-G) was significantly lower at 2 months (31% v 48%; P = .016) and 12 months (19% v 38%; P = .009). In group T, the Hospital Anxiety and Depression Scale score (P = .003) and the proportion of severe sensory peripheral neuropathy (P = .001) were significantly lower at 2 months, and Philadelphia Geriatric Center Morale Scale and Tokyo Metropolitan Institute of Gerontology Index of Competence scores were significantly higher (P = .024, .042) at 12 months. At 36 months, there were no significant differences in any QoL items. Detrimental effects of adjuvant chemotherapy on global QoL, morale, and activity capacity lasted for at least 12 months but were not observed at 36 months.

Validation of the Patient Neurotoxicity Questionnaire for Patients Suffering From Chemotherapy-Induced Peripheral Neuropathy in Greek.

Purpose: The Patient Neurotoxicity Questionnaire (PNQ) represents a diagnostic tool concerning patients with chemotherapy-induced peripheral neuropathy (CIPN). The application of such a tool in the Greek clinical praxis requires validation.Methods: Validation consists of three stages - translation, reverse translation, and patient application. Hundred oncologic patients were assessed by comparing the PNQ to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) at the chemotherapy onset and second, fourth, and sixth sessions. The diagnostic tool's specific requirements (compliance, validity, concordance, sensitivity, specificity, reliability) were statistically evaluated.Results: Differences between translated texts and between the reverse translation and the original were considered negligible. At the second, fourth, and sixth session compliance was 98%, 95%, and 93% while Cronbach’s α was 0,57 0,69, and 0,81, respectively. Cohen’s weighted κ was 0,67 and 0,58, Spearman’s ρ was 0,7 and 0,98, while the area under the curve (AUC) of the receiver operating characteristic (ROC) was 1 and 0,9 for the sensory and the motor part, respectively. The variance’s linear regression analysis confirmed CIPN worsening over time (P<0.0001).Discussion: The Greek version remains close to the original English version. Compliance rates reflect easy PNQ applications. Cohen’s κ values highlight the physicians’ tension to underestimate the patients’ condition. Spearman’s ρ, Cronbach’s α, and AUC values reflect good validity, reliability, and specificity of the PNQ respectively. Finally, the linear analysis confirmed the PNQ sensitivity over time.Conclusions: The PNQ validation in Greek adds a crucial tool to the physicians' armamentarium. It can now delineate the necessary information to modify the chemotherapy and analgesic treatment regimens at both preventive and acute levels.

Chemotherapy-Induced Peripheral Neurotoxicity as A Risk Factor for Poor Sleep Quality in Breast Cancer Survivors Treated with Docetaxel

Objective:The purpose of this study was to explore sleep quality and to determine whether chemotherapy-induced peripheral neurotoxicity is a risk factor for poor sleep quality in breast cancer survivors who receive docetaxel treatment.Methods:Secondary data analysis from a cross-sectional study. Sample characteristics were collected using an information sheet. Independent variables included the Hospital Anxiety and Depression Scale (HADS), the Patient Neurotoxicity Questionnaire (PNQ), and the Identification Pain Questionnaire (ID pain). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). We performed descriptive analyses and simple logistic regression.Results:A total of 98 participants were included. More than 60% of them reported poor sleep quality, with their average PSQI score being 7.54 ± 4.45. Poor subjective sleep quality (1.37 ± 0.88) and short sleep duration (1.37 ± 1.08) were their main problems. In addition, significant risk factors for poor sleep quality were chronic illness (odds ratio [OR] = 2.753, P = 0.041), anxiety (OR = 7.714, P = 0.009), neuropathic pain (OR = 11.261, P = 0.022), sensory neuropathy (OR = 2.529, P = 0.032), motor neuropathy (OR = 3.781, P = 0.002), and undergoing chemotherapy (OR = 2.593, P = 0.027). Targeted therapy that some survivors received served as a protective factor (OR = 0.351, P = 0.015).Conclusions:We found a high prevalence of poor sleep quality in breast cancer survivors treated with docetaxel. The results indicated that, in addition to clinical characteristics and psychological discomfort, chemotherapy-induced peripheral neurotoxicity is a significant risk factor for poor sleep quality.

Abstract P2-16-07: Randomized controlled trial of neoadjuvant eribulin mesylate versus paclitaxel in women with operable breast cancer (JONIE-3 study)

Abstract Background: Eribulin mesylate (ERI) improved the overall survival in metastatic breast cancer (BC) patients. However, the efficacy has not been reported in early breast cancer. We performed the neoadjuvant chemotherapy (NAC) study based on hypothesis that ERI is less toxic, particularly in peripheral neuropathy, and has similar efficacy to paclitaxel (PTX) in patients with operable BC. Methods: This is a multicenter open label randomized phase 2 study (UMIN000012817). Patients were randomly assigned to either ERI (1.4mg/m2, d1 and d8, q21 days, 4 cycles) followed by FEC (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2) (ERI-FEC) or PTX (80mg/m2, weekly, 12 cycles) followed by FEC (PTX-FEC) with stratified by ER, HER2, and menopausal status. Trastuzumab was added in patients with HER2 positive disease. Primary endpoint was the incidence of peripheral sensory and motor neuropathy (PSN and PMN) with Grade 1 or higher according to CTCAE ver.4.0. Secondary endpoints were pathological complete response (pCR) rates (ypT0/is/ypN0), clinical response rates (CR+PR), adverse events, disease-free survival (DFS) and patient neurotoxicity questionnaire (PNQ) analysis. Here, we report 3 year’s DFS and PNQ analysis in this study Results: Between December 2013 to March 2016, 121 cases were enrolled and 5 cases were excluded from the primary assessment. One hundred sixteen cases were finally randomized and treated by ERI-FEC in 58 cases and PTX-FEC in 57 cases. A median follow-up time of ERI-FEC and PTX-FEC was 54.2 and 51.4 months, respectively. Three year-DFS rate were 89.7% in the ERI-FEC group (95% CI 51.1 - 57.3) and 86.0% in the PTX-FEC group. (p=0.561). The incidences of PSN and PMN were significantly lower in the ERI-FEC group than the PAX-FEC group at the end of treatments (previously reported). PNQ analysis after treatments is now undergone. Conclusion: DFS was not different between them. Although the pCR rate was lower in ERI-FEC than PAC-FEC as reported at the previous meeting. ERI was more favorable on adverse events than PTX during NAC treatments. Long-term results on neurotoxicity of these two drugs will be presented at the meeting. Citation Format: Takahiko Kawate, Takashi Ishikawa, Daishu Miura, Yoshie Hasegawa, Akihiko Tachibana, Jun Horiguchi, Mitsuhiro Hayashi, Masaru Miyashita, Tomoyuki Kubota, Kazutaka Narui, Masato Suzuki, Kouhei Akazawa, Norio Kohno. Randomized controlled trial of neoadjuvant eribulin mesylate versus paclitaxel in women with operable breast cancer (JONIE-3 study) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-07.

Abstract P2-15-04: Patient-reported outcomes in a randomized, optimal dose finding, phase II study of triweekly nab-paclitaxel in patients with metastatic breast cancer (the ABROAD study)

Abstract OBJECTIVE: Nab-paclitaxel (nab-PTX) has superior efficacy compared to conventional paclitaxel in metastatic breast cancer (MBC), but chemotherapy-induced peripheral neuropathy (CIPN) is more frequent with nab-PTX. In a single arm phase 2 trial (CA002-0LD), low dose nab-PTX (175 mg/m2) every 3 weeks (q3w) resulted in a good objective response rate (39.5%) without CIPN of grade 3 or higher. Therefore, we conducted a randomized controlled study to evaluate the optimal dose of nab-PTX by comparing a low dose (LD) and a medium dose (MD) to the standard dose (SD). Here, we evaluate the patients-reported outcomes (PROs) and health-related quality of life (HRQoL) in the ABROAD study. PATIENTS AND METHODS: Three different doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2) were administered in patients with HER2-negative metastatic breast cancer. The primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates with the three doses were estimated by logistic regression. The optimal dose was selected by 2-step selection. First, if the hazard ratio (HR) for PFS was &amp;lt;0.75 or &amp;gt;1.33, the inferior dose was dropped. Then, a dose with an estimated incidence of grade 3/4 neurotoxicity &amp;gt;10% was also dropped. PROs and HRQoL were assessed as secondary endpoints at baseline, and during the 2nd, 4th and 6th courses of protocol treatment using the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane), Patient Neurotoxicity Questionnaire (PNQ), Cancer Fatigue Scale (CFS) and EuroQol 5 Dimension (EQ-5D). The primary outcome for PROs and HRQoL was the FACT-Taxane trial outcome index (TOI), and inter-group comparison was performed using a mixed effect model for repeated measures (MMRM). This trial was registered with the University Hospital Medical Information Network (UMIN), Japan (protocol ID C000012429). RESULTS: A total of 141 patients were randomly assigned to SD (n=47), MD (n=46) or LD (n=48) nab-PTX. PFS analysis showed that LD nab-PTX at 180 mg/m2/3 weeks was the optimal dose with good clinical efficacy and tolerability for patients with MBC (reported by Hara at ASCO2019). Longitudinal analysis (MMRM) showed that the difference from the baseline FACT-Taxane TOI score at MD and LD were significantly better than that at SD (MD vs. SD p&amp;lt;0.001, LD vs. SD p&amp;lt;0.001). Differences from baseline for the FACT-Taxane total score, physical well-being sub-score, and emotional well-being sub-score at MD and LD were also better than at SD. The difference from baseline for the CFS score at LD was better than that at SD (p=0.013) and those for EQ-5D utility scores at MD and LD were better than that at SD (MD vs. SD p=0.011, LD vs. SD p&amp;lt;0.001). There were no significant differences for the PNQ. CONCLUSION: Our results show that low dose nab-PTX at 180 mg/m2/3 weeks could be an optimal dose for PFS and from the perspectives of PROs and HRQoL. Citation Format: Hiroaki Kato, Fumikata Hara, Masahiro Kitada, Masato Takahashi, Yuichiro Kikawa Yuichiro Kikawa, Eiko Sakata, Yoichi Naito, Yoshie Hasegawa, Tsuyoshi Saito, Tsutomu Iwasa, Junji Tsurutani, Naruto Taira, Tsutomu Takashima, Kosuke Kashiwabara, Tomohiko Aihara Tomohiko Aihara, Hirofumi Mukai. Patient-reported outcomes in a randomized, optimal dose finding, phase II study of triweekly nab-paclitaxel in patients with metastatic breast cancer (the ABROAD study) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-04.

Abstract PD10-02: Patient reported outcomes from the adjuvant trastuzumab emtansine (T-DM1) vs. paclitaxel + trastuzumab (TH) (ATEMPT) trial (TBCRC 033)

Abstract Purpose: The ATEMPT trial sought to determine if adjuvant T-DM1 (every 3 wks for 1 yr) for Stage I HER2 positive breast cancer is better tolerated than TH (paclitaxel weekly x 12 wks with 1 yr of trastuzumab). Here we compare patient-reported outcomes (PROs) including quality of life (QOL), specific symptoms, and work productivity between the two treatments over time. Patients and Methods: English-speaking patients were randomized (3:1) to T-DM1 or TH, and completed PRO assessments at baseline (day 1), 3 wks, 12 wks, and 6, 12, and 18 mos after initiation of treatment. Surveys included the FACT-B, Patient-Neurotoxicity Questionnaire (PNQ), Rotterdam Symptom Checklist (RSCL), Alopecia Patient Assessment, and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP). Results: 469/497 (94%) patients (363 on T-DM1, 106 on TH) completed surveys at any timepoint, ranging from 100% at baseline to 79% at 18 mos. Median age was 56 yrs (range 23-85). There were different patterns of deterioration and recovery seen over time in each group for QOL and other relevant symptoms. Compared with the T-DM1 group, the TH group had significantly lower mean total FACT-B scores, indicating poorer QOL from baseline to 12 weeks (p&amp;lt;0.001 for each timepoint); mean scores were similar between the groups at 6 and 12 mos, and significantly worse again in the TH group at 18 mos. The greatest mean change from baseline, and lowest FACT-B scores overall were reported in the TH group at 12 weeks. Moderate to severe sensory neuropathy was 8% at 12 weeks for patients receiving T-DM1 and reached its highest level of 15% by 18 mos. In comparison, moderate to severe sensory neuropathy was 35% at 12 weeks and 26% at 18 mos for patients on TH (p&amp;lt;0.001 at 12 weeks and p=0.018 at 18 mos). Hair loss at week 12 was 13% on T-DM1 compared to 77% on TH (p&amp;lt;0.001). Mean physical symptom distress was greater for TH at baseline, 3 and 12 weeks, and greater for T-DM1 at 1 year, with greatest symptom distress reported by the TH group at 12 weeks. Psychological distress was greatest for both groups at enrollment, though significantly greater with TH than T-DM1 at baseline, 12 weeks and 18 mos (groups were similar at 6 and 12 mos). There was limited impact on activity level impairment in both groups. Rates of employment were lowest for the TH group at 12 weeks (49% TH vs. 61% T-DM1, p=0.074) with significant differences seen at 3 and 12 weeks for percent work time missed due to health treatment, percent impairment while working, percent overall work impairment, and percent activity impairment, all favoring T-DM1. Conclusion: PROs differ between patients with Stage I HER2 positive breast cancer treated with T-DM1 vs. TH. T-DM1 treated patients had better QOL, less neuropathy and hair loss, and better work productivity, particularly during the first 12 weeks of treatment, and importantly, differences persist with longer-term follow-up. Citation Format: Ann Partridge, Yue Zheng, Shoshana Rosenberg, Richard Gelber, Shari Gelber, William Barry, Chau Dang, Denise Yardley, Steven Isakoff, Vicente Valero, Meredith Faggen, Therese Mulvey, Ron Bose, Douglas Weckstein, Antonio Wolff, Katherine Reeder-Hayes, Hope Rugo, Bhuvaneswari Ramaswamy, Dan Zuckerman, Lowell Hart, Vijayakrishna Gadi, Michael Constantine, Kit Cheng, Frederick Briccetti, Bryan Schneider, Merrill Garrett, P. Kelly Marcom, Kathy Albain, Patricia Defusco, Nadine Tung, Blair Ardman, Rita Nanda, Rachel Jankowitz, Michelle DeMeo, Harold Burstein, Eric P. Winer, Ian Krop, Sara Tolaney. Patient reported outcomes from the adjuvant trastuzumab emtansine (T-DM1) vs. paclitaxel + trastuzumab (TH) (ATEMPT) trial (TBCRC 033) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD10-02.

Cryotherapy for the prevention of weekly paclitaxel-induced peripheral adverse events in breast cancer patients

PurposeThis randomized phase II study was conducted to investigate the efficacy of cryotherapy in preventing peripheral neuropathy and dermatological adverse events in breast cancer patients treated with weekly paclitaxel.MethodsPatients treated with 12 weekly doses of paclitaxel for breast cancer were randomized (1:1) into a cryotherapy or control group. The primary endpoint was the percentage of patients with a marked decrease in the Functional Assessment of Cancer Therapy-Neurotoxicity (FACT-NTX) score. The secondary endpoints were Patient Neurotoxicity Questionnaire (PNQ), Common Terminology Criteria for Adverse Event (CTCAE) for peripheral neuropathy, and FACT-Taxane score.ResultsForty-four patients were randomly assigned to the cryotherapy (n = 22) or control groups (n = 22). The percentage of patients with a marked decrease in FACT-NTX scores was significantly lower in the cryotherapy group than in the control group (41 vs. 73%, p = 0.03). The incidence of CTCAE grade ≥ 2 sensory (p = 0.001) and motor peripheral neuropathy (p = 0.01), and PNQ grade D or higher for sensory peripheral neuropathy (p = 0.02), and decrease in the FACT-Taxane score (p = 0.02) were also significantly lower in the cryotherapy group than in the control group. There were no serious side effects associated with cryotherapy.ConclusionCryotherapy is an effective approach for prevention of peripheral neuropathy and dermatological adverse events in breast cancer patients treated with weekly paclitaxel.

Impact of Ninjin'Yoeito on Fatigue in Patients Receiving Nab-Paclitaxel Plus Gemcitabine Therapy: A Prospective, Single-Arm, Phase II Open Label, Nonrandomized, Historically-Controlled Study

BackgroundNinjin'yoeito, a traditional Japanese herbal medicine, is used to prevent fatigue, loss of appetite, and coldness of limbs. Fatigue is an especially common issue during chemotherapy and can affect quality of life and the ability to complete scheduled treatment.ObjectivesThis prospective exploratory trial evaluates the efficacy of ninjin'yoeito for fatigue in patients undergoing nab-paclitaxel plus gemcitabine therapy for unresectable pancreatic cancer. The primary end point was evaluation of fatigue according to Functional Assessment of Chronic Illness Therapy-Fatigue score during 2 courses of nab-paclitaxel plus gemcitabine therapy. Secondary end points included evaluation of dose intensity, appetite loss using numerical rating scale, and peripheral neuropathy using a patient neurotoxicity questionnaire.MethodsWe compared data from this interventional trial with a prior observational trial without administration of ninjin'yoeito with identical definition of end points (UMIN000021758). Thirty patients were required by the study.ResultsThreshold mean of Functional Assessment of Chronic Illness Therapy-Fatigue score across 8 weeks during chemotherapy was under 5.3 (P = 0.002). Secondary end points did not reveal any specific patterns in appetite loss or degree of pain. No significant changes in patient neurotoxicity questionnaire concerning sensory/motor disorders were observed, but the mean (SD) incidence of patients with sensory disturbance was higher between the fifth and eighth weeks (8.8 [1.26]) than during the first and fourth weeks (4.8 [0.96]) (P = 0.003). Clinically significant adverse reactions of ninjin'yoeito were not observed.ConclusionsNinjin'yoeito may be useful for improving the symptoms of fatigue caused by nab-paclitaxel plus gemcitabine in patients with unresectable pancreatic cancer. UMIN Clinical Trials Registry identifier: UMIN000025606. (Curr Ther Res Clin Exp. 2020; 81:XXX–XXX)

Hand and foot exercises for diabetic peripheral neuropathy: A randomized controlled trial.

Exercises for diabetic peripheral neuropathy remain controversial, especially with regard to recommended precautions and weightbearing exercises for individuals. We aimed to investigate the effect of 8 weeks of simple hand, finger, and foot exercises in patients with diabetic peripheral neuropathy. After randomization, exercise (n = 51) and control (n = 53) groups received usual care and diabetic foot care education; only the exercise group performed exercises. Primary outcomes, including activities of daily living (assessed using the Patient Neurotoxicity Questionnaire), neuropathy severity (monofilament and vibration test), and pain (behavioral rating scale and Visual Analog Scale), and secondary outcomes, including physical function of the hand and foot (grip, pinch, finger counting time, and Timed Up and Go tests), were assessed at baseline, after the 8-week intervention, and at the 16-week follow-up. The exercise group showed significantly stronger improvements in motor score and specific activities of daily living, such as climbing stairs and performing work or chores. Our exercises can be used to improve limb function in patients with diabetic neuropathy.