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Personalized Management of Chemotherapy-Induced Peripheral Neuropathy Based on a Patient Reported Outcome: CALGB 40502 (Alliance).

  • Sharma, Manish R1
  • Mehrotra, Shailly2
  • Gray, Elizabeth1
  • Wu, Kehua1
  • Barry, William T3
  • Hudis, Clifford4
  • Winer, Eric P5
  • Lyss, Alan P6
  • Toppmeyer, Deborah L7
  • Moreno-Aspitia, Alvaro8
  • Lad, Thomas E9
  • Velasco, Mario10
  • Overmoyer, Beth5
  • Rugo, Hope S11
  • Ratain, Mark J1
  • Gobburu, Jogarao V2
  • 1 The University of Chicago, Chicago, Illinois, USA.
  • 2 Center for Translational Medicine, University of Maryland, Baltimore, Maryland, USA.
  • 3 Alliance Statistics and Data Center, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
  • 4 Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • 5 Dana-Farber/Partners CancerCare/Harvard Cancer Center, Boston, Massachusetts, USA.
  • 6 Heartland Cancer Research NCORP, St. Louis, Missouri, USA.
  • 7 Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA. , (Jersey)
  • 8 Mayo Clinic, Jacksonville, Florida, USA.
  • 9 John H. Stroger Jr Hospital of Cook County, Chicago, Illinois, USA.
  • 10 Decatur Memorial Hospital/Cancer Care Specialists of Illinois/Heartland Cancer Research NCORP, Decatur, Illinois, USA.
  • 11 University of California San Francisco, San Francisco, California, USA.
Published Article
Journal of clinical pharmacology
Publication Date
Dec 04, 2019
DOI: 10.1002/jcph.1559
PMID: 31802506


Chemotherapy-induced peripheral neuropathy (henceforth, neuropathy) is often dose limiting and is generally managed by empirical dose modifications. We aimed to (1) identify an early time point that is predictive of future neuropathy using a patient-reported outcome and (2) propose a dose-adjustment algorithm based on simulated data to manage neuropathy. In previous work, a dose-neuropathy model was developed using dosing and patient-reported outcome data from Cancer and Leukemia Group B 40502 (Alliance), a randomized phase III trial of paclitaxel, nanoparticle albumin-bound paclitaxel or ixabepilone as first-line chemotherapy for locally recurrent or metastatic breast cancer. In the current work, an early time point that is predictive of the future severity of neuropathy was identified based on predictive accuracy of the model. Using the early data and model parameters, simulations were conducted to propose a dose-adjustment algorithm for the prospective management of neuropathy in individual patients. The end of the first 3 cycles (12 weeks) was identified as the early time point based on a predictive accuracy of 75% for the neuropathy score after 6 cycles. For paclitaxel, nanoparticle albumin-bound paclitaxel, and ixabepilone, simulations with the proposed dose-adjustment algorithm resulted in 61%, 48%, and 35% fewer patients, respectively, with neuropathy score ≥8 after 6 cycles compared to no dose adjustment. We conclude that early patient-reported outcome data on neuropathy can be used to guide dose adjustments in individual patients that reduce the severity of future neuropathy. Prospective validation of this approach should be undertaken in future studies. © 2019, The American College of Clinical Pharmacology.

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