Hemoglobin, Body Mass Index, and Age as Risk Factors for Paclitaxel- and Oxaliplatin-Induced Peripheral Neuropathy

Mizrahi, David; Park, Susanna B.; Li, Tiffany; Timmins, Hannah C.; Trinh, Terry; Au, Kimberley; Battaglini, Eva; Wyld, David; Henderson, Robert D.; Grimison, Peter; Ke, Helen; Geelan-Small, Peter; Marker, Julie; Wall, B.; Goldstein, David

doi:10.1001/jamanetworkopen.2020.36695

Cited by 67 publications

(69 citation statements)

References 64 publications

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“…Mizrahi et al carried out a large cross-sectional study including 105 patients treated with OXA. The results showed a correlation between reduced pretreatment levels of hemoglobin, detected in 24.5% of the cohort, with a greater severity of neuropathy [ 14 ]. In addition, previous studies on patients receiving OXA concluded similar results [ 15 , 19 , 22 , 27 ].…”

Section: Blood Biomarkersmentioning

confidence: 99%

“…Among pretreatment metabolic and nutritional blood-based biomarkers, there are conflicting results. Such as higher albumin level [ 14 ] as hypoalbuminemia [ 15 , 19 ] have been associated with the risk of developing OXAIPN. Despite higher rates of neurotoxicity were described in patients with low levels of magnesium, the lack of evidence in this line [ 14 ] would support the known inefficacy of calcium-magnesium supplementation during OXA treatment as a neuroprotective approach [ 9 ].…”

Section: Blood Biomarkersmentioning

confidence: 99%

“…Importantly, the observed worsening of OXAIPN weeks after cessation of treatment complicates clinical decisions regarding the duration and total dose of OXA in individual patients based on symptoms of sensory neuropathy alone. Cumulative dose of OXA is the main predictor of OXAIPN [12][13][14], with increasing rates from 42.5% to 76.7% with median cumulative dose of ≤780 mg/m 2 and >780 mg/m 2 , respectively [11], also when re-challenging patients with OXA in further lines [15,16]. However, the relationship between dose and neurotoxicity might not be linear before reaching a cumulative dose level beyond which the toxicity becomes dose-dependent [17].…”

Section: Introductionmentioning

confidence: 99%

“…From the personalized medicine perspective, having non-invasive, sensitive and specific biomarkers, will allow patients more liable to OXAIPN to prevent the occurrence of long-term toxicity or permanent damage. These objective markers may aid in the prediction of the development, severity and duration OXAIPN, and in adjusting OXA dose more precisely to balance the risk of neurotoxicity against antineoplastic effi- Cumulative dose of OXA is the main predictor of OXAIPN [12][13][14], with increasing rates from 42.5% to 76.7% with median cumulative dose of ≤780 mg/m 2 and >780 mg/m 2 , respectively [11], also when re-challenging patients with OXA in further lines [15,16]. However, the relationship between dose and neurotoxicity might not be linear before reaching a cumulative dose level beyond which the toxicity becomes dose-dependent [17].…”

Section: Introductionmentioning

confidence: 99%

“…Cumulative dose of OXA is the main predictor of OXAIPN [ 12 , 13 , 14 ], with increasing rates from 42.5% to 76.7% with median cumulative dose of ≤780 mg/m 2 and >780 mg/m 2 , respectively [ 11 ], also when re-challenging patients with OXA in further lines [ 15 , 16 ]. However, the relationship between dose and neurotoxicity might not be linear before reaching a cumulative dose level beyond which the toxicity becomes dose-dependent [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Predictive Biomarkers of Oxaliplatin-Induced Peripheral Neurotoxicity

Velasco

Alemany

Villagrán

et al. 2021

JPM

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Oxaliplatin (OXA) is a platinum compound primarily used in the treatment of gastrointestinal cancer. OXA-induced peripheral neurotoxicity (OXAIPN) is the major non-hematological dose-limiting toxicity of OXA-based chemotherapy and includes acute transient neurotoxic effects that appear soon after OXA infusion, and chronic non-length dependent sensory neuronopathy symmetrically affecting both upper and lower limbs in a stocking-and-glove distribution. No effective strategy has been established to reverse or treat OXAIPN. Thus, it is necessary to early predict the occurrence of OXAIPN during treatment and possibly modify the OXA-based regimen in patients at high risk as an early diagnosis and intervention may slow down neuropathy progression. However, identifying which patients are more likely to develop OXAIPN is clinically challenging. Several objective and measurable early biomarkers for OXAIPN prediction have been described in recent years, becoming useful for informing clinical decisions about treatment. The purpose of this review is to critically review data on currently available or promising predictors of OXAIPN. Neurological monitoring, according to predictive factors for increased risk of OXAIPN, would allow clinicians to personalize treatment, by monitoring at-risk patients more closely and guide clinicians towards better counseling of patients about neurotoxicity effects of OXA.

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Section: Blood Biomarkersmentioning

confidence: 99%

Section: Blood Biomarkersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Predictive Biomarkers of Oxaliplatin-Induced Peripheral Neurotoxicity

Velasco

Alemany

Villagrán

et al. 2021

JPM

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Association of Taxane Type With Patient-Reported Chemotherapy-Induced Peripheral Neuropathy Among Patients With Breast Cancer

Yan

Zhao

et al. 2022

JAMA Netw Open

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ImportanceUnderstanding the detailed symptom spectrum of chemotherapy-induced peripheral neuropathy (CIPN) could facilitate shared decision-making and promote early intervention.ObjectiveTo compare the symptom spectrum of patient-reported CIPN associated with nab-paclitaxel, paclitaxel, and docetaxel treatments among patients with breast cancer.Design, Setting, and ParticipantsThis 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.ExposuresTreatment with nab-paclitaxel–, paclitaxel-, or docetaxel-based regimens.Main Outcomes and MeasuresPatient-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.ResultsOf 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 &lt; .001) or docetaxel (HR, 0.52 [95% CI, 0.36-0.75]; P &lt; .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.Conclusions and RelevanceIn 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.

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Exploratory randomized phase II trial for optimizing treatment dosage and duration of adjuvant S‐1 plus oxaliplatin in patients with stage III colon cancer: YCOG1402 (SOAP trial)

Suwa

Watanabe

Suwa

et al. 2023

Annals of Gastroent Surgery

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IntroductionConventionally, the recommended duration of adjuvant chemotherapy of colon cancer had been 6 months. The IDEA Collaboration suggested that shortening capecitabin and oxaliplatin (CAPOX) adjuvant chemotherapy may be possible. S‐1 and oxaliplatin (SOX) treatment is standard treatment in metastatic colorectal cancer in Japan. The aim of this study was to optimize treatment dosage and duration of adjuvant SOX in stage III colon cancer.MethodsThis trial was as open‐label multi‐center randomized phase II study. Patients with stage III colon cancer were randomly assigned to 3 months or 6 months of adjuvant SOX treatment in different doses: 130 mg/m2 (3 months) or 100 mg/m2 (6 months) of oxaliplatin. The primary endpoint was 3‐year disease‐free survival (DFS) and the null hypothesis for the primary endpoint was that the 3‐year DFS was ≤72% in each arm and was tested with a one‐sided significance level of 10%.ResultsEighty‐two patients were assigned to the 6 months arm and 81 to the 3 months arm. The 3‐year DFS was 75.0% (80% CI 67.95–80.72, p = 0.282) in the 6 months arm and 76.9% (80% CI 70.1–82.38, p = 0.171) in the 3 months arm. Treatment completion rate and relative dose intensity (RDI) were higher in 3 months than 6 months arm. The adverse events (AE) were similar in both arms.ConclusionsThe 3‐year DFS was not significantly superior to null hypothesis in both 3 months and 6 months arms for the stage III colon cancer. Primary endpoint was not achieved. The SOX regimen was not feasible in long‐term outcomes.

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Hemoglobin, Body Mass Index, and Age as Risk Factors for Paclitaxel- and Oxaliplatin-Induced Peripheral Neuropathy

Cited by 67 publications

References 64 publications

Predictive Biomarkers of Oxaliplatin-Induced Peripheral Neurotoxicity

Predictive Biomarkers of Oxaliplatin-Induced Peripheral Neurotoxicity

Association of Taxane Type With Patient-Reported Chemotherapy-Induced Peripheral Neuropathy Among Patients With Breast Cancer

Exploratory randomized phase II trial for optimizing treatment dosage and duration of adjuvant S‐1 plus oxaliplatin in patients with stage III colon cancer: YCOG1402 (SOAP trial)

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