Ciao-Sin Chen1, Ellen M Lavoie Smith2, Kathleen A Stringer1,3, N Lynn Henry4, Daniel L Hertz5,6. 1. Department of Clinical Pharmacy, University of Michigan College of Pharmacy, 428 Church St., Room 3054, Ann Arbor, MI, 48109-1065, USA. 2. University of Alabama at Birmingham School of Nursing, Birmingham, AL, USA. 3. NMR Metabolomics Laboratory, University of Michigan College of Pharmacy, Ann Arbor, MI, USA. 4. University of Michigan Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA. 5. Department of Clinical Pharmacy, University of Michigan College of Pharmacy, 428 Church St., Room 3054, Ann Arbor, MI, 48109-1065, USA. DLHertz@med.umich.edu. 6. University of Michigan Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA. DLHertz@med.umich.edu.
Abstract
PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is the major treatment-limiting toxicity of paclitaxel, which predominantly presents as sensory symptoms, with motor symptoms in some patients. Differentiating CIPN into subtypes has been recommended to direct CIPN research. The objective of this study was to investigate whether sensory and motor CIPN are distinct subtypes with different predictive biomarkers in patients with breast cancer receiving paclitaxel. METHODS: Data were from a prospective cohort of 60 patients with breast cancer receiving up to 12 weekly infusions of 80 mg/m2 paclitaxel (NCT02338115). European Organisation for Research and Treatment of Cancer Quality of Life questionnaire CIPN20 was used to evaluate CIPN. Clusters of the time course of sensory (CIPNS), motor (CIPNM), and the difference between sensory and motor (CIPNS-CIPNM) were identified using k-means clustering on principal component scores. Predictive metabolomic biomarkers of maximum CIPNS and CIPNM were investigated using linear regressions adjusted for baseline CIPN, paclitaxel pharmacokinetics, and body mass index. RESULTS: More sensory than motor CIPN was found (CIPNS change: mean = 10.8, ranged [-3.3, 52.1]; CIPNM change: mean = 3.5, range: [-7.5, 35.0]). Three groups were identified with No CIPN, Mixed CIPN, and Sensory-dominant CIPN (maximum CIPNS: mean = 12.7 vs. 40.9 vs. 74.3, p < 0.001; maximum CIPNM: mean = 5.4 vs. 25.5 vs. 36.1, p < 0.001; average CIPNS-CIPNM: mean = 2.8 vs. 5.8 vs. 24.9, p < 0.001). Biomarkers of motor CIPN were similar to previously identified biomarkers of sensory CIPN, including lower serum histidine (p = 0.029). CONCLUSION: Our findings suggest that sensory and motor CIPN co-occur and may not have differentiating metabolic biomarkers. These findings need to be validated in larger cohorts of patients treated with paclitaxel and other neurotoxic agents to determine the optimal approach to predict, prevent, and treat CIPN and improve patients' outcomes.
PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is the major treatment-limiting toxicity of paclitaxel, which predominantly presents as sensory symptoms, with motor symptoms in some patients. Differentiating CIPN into subtypes has been recommended to direct CIPN research. The objective of this study was to investigate whether sensory and motor CIPN are distinct subtypes with different predictive biomarkers in patients with breast cancer receiving paclitaxel. METHODS: Data were from a prospective cohort of 60 patients with breast cancer receiving up to 12 weekly infusions of 80 mg/m2 paclitaxel (NCT02338115). European Organisation for Research and Treatment of Cancer Quality of Life questionnaire CIPN20 was used to evaluate CIPN. Clusters of the time course of sensory (CIPNS), motor (CIPNM), and the difference between sensory and motor (CIPNS-CIPNM) were identified using k-means clustering on principal component scores. Predictive metabolomic biomarkers of maximum CIPNS and CIPNM were investigated using linear regressions adjusted for baseline CIPN, paclitaxel pharmacokinetics, and body mass index. RESULTS: More sensory than motor CIPN was found (CIPNS change: mean = 10.8, ranged [-3.3, 52.1]; CIPNM change: mean = 3.5, range: [-7.5, 35.0]). Three groups were identified with No CIPN, Mixed CIPN, and Sensory-dominant CIPN (maximum CIPNS: mean = 12.7 vs. 40.9 vs. 74.3, p < 0.001; maximum CIPNM: mean = 5.4 vs. 25.5 vs. 36.1, p < 0.001; average CIPNS-CIPNM: mean = 2.8 vs. 5.8 vs. 24.9, p < 0.001). Biomarkers of motor CIPN were similar to previously identified biomarkers of sensory CIPN, including lower serum histidine (p = 0.029). CONCLUSION: Our findings suggest that sensory and motor CIPN co-occur and may not have differentiating metabolic biomarkers. These findings need to be validated in larger cohorts of patients treated with paclitaxel and other neurotoxic agents to determine the optimal approach to predict, prevent, and treat CIPN and improve patients' outcomes.
Authors: Marta Seretny; Gillian L Currie; Emily S Sena; Sabrina Ramnarine; Robin Grant; Malcolm R MacLeod; Leslie A Colvin; Marie Fallon Journal: Pain Date: 2014-09-23 Impact factor: 6.961
Authors: Theodore S Jennaro; Fang Fang; Kelley M Kidwell; Ellen M Lavoie Smith; Kiran Vangipuram; Monika L Burness; Jennifer J Griggs; Catherine Van Poznak; Daniel F Hayes; N Lynn Henry; Daniel L Hertz Journal: Breast Cancer Res Treat Date: 2020-03-12 Impact factor: 4.872
Authors: Jennifer S Gewandter; Joanna Brell; Guido Cavaletti; Patrick M Dougherty; Scott Evans; Lynn Howie; Michael P McDermott; Ann O'Mara; A Gordon Smith; Daniela Dastros-Pitei; Lynn R Gauthier; Simon Haroutounian; Matthew Jarpe; Nathaniel P Katz; Charles Loprinzi; Paul Richardson; Ellen M Lavoie-Smith; Patrick Y Wen; Dennis C Turk; Robert H Dworkin; Roy Freeman Journal: Neurology Date: 2018-07-27 Impact factor: 9.910
Authors: Heather E Wheeler; Eric R Gamazon; Claudia Wing; Uchenna O Njiaju; Chidiamara Njoku; Robert Michael Baldwin; Kouros Owzar; Chen Jiang; Dorothy Watson; Ivo Shterev; Michiaki Kubo; Hitoshi Zembutsu; Eric P Winer; Clifford A Hudis; Lawrence N Shulman; Yusuke Nakamura; Mark J Ratain; Deanna L Kroetz; Nancy J Cox; Mary Eileen Dolan Journal: Clin Cancer Res Date: 2012-11-30 Impact factor: 12.531
Authors: Ting Bao; Coby Basal; Christina Seluzicki; Susan Q Li; Andrew D Seidman; Jun J Mao Journal: Breast Cancer Res Treat Date: 2016-08-10 Impact factor: 4.872