A quantitative sensory analysis of peripheral neuropathy in colorectal cancer and its exacerbation by oxaliplatin chemotherapy

Mariana De Carvalho Barbosa, Alyssa K. Kosturakis, Cathy Eng, Gwen Wendelschafer-Crabb, William R Kennedy, Donald A Simone, Xin S. Wang, Charles S. Cleeland, Patrick M. Dougherty

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Peripheral neuropathy caused by cytotoxic chemotherapy, especially platins and taxanes, is a widespread problemamong cancer survivors that is likely to continue to expand in the future. However, little work to date has focused on understanding this challenge. The goal in this study was to determine the impact of colorectal cancer and cumulative chemotherapeutic dose on sensory function to gain mechanistic insight into the subtypes of primary afferent fibers damaged by chemotherapy. Patients with colorectal cancer underwent quantitative sensory testing before and then prior to each cycle of oxaliplatin. These data were compared with those from 47 age- and sex-matched healthy volunteers. Patients showed significant subclinical deficits in sensory function before any therapy compared with healthy volunteers, and they became more pronounced in patients who received chemotherapy. Sensory modalities that involved large Aβ myelinated fibers and unmyelinated C fibers were most affected by chemotherapy, whereas sensory modalities conveyed by thinly myelinated Aδ fibers were less sensitive to chemotherapy. Patients with baseline sensory deficits went on to develop more symptom complaints during chemotherapy than those who had no baseline deficit. Patients who were tested again 6 to 12 months after chemotherapy presented with the most numbness and pain and also the most pronounced sensory deficits. Our results illuminate a mechanistic connection between the pattern of effects on sensory function and the nerve fiber types that appear to be most vulnerable to chemotherapy-induced toxicity, with implications for how to focus future work to ameloirate risks of peripheral neuropathy.

Original languageEnglish (US)
Pages (from-to)5955-5962
Number of pages8
JournalCancer Research
Volume74
Issue number21
DOIs
StatePublished - Nov 1 2014

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oxaliplatin
Peripheral Nervous System Diseases
Colorectal Neoplasms
Drug Therapy
Healthy Volunteers
Myelinated Nerve Fibers
Taxoids
Unmyelinated Nerve Fibers
Hypesthesia
Nerve Fibers

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A quantitative sensory analysis of peripheral neuropathy in colorectal cancer and its exacerbation by oxaliplatin chemotherapy. / De Carvalho Barbosa, Mariana; Kosturakis, Alyssa K.; Eng, Cathy; Wendelschafer-Crabb, Gwen; Kennedy, William R; Simone, Donald A; Wang, Xin S.; Cleeland, Charles S.; Dougherty, Patrick M.

In: Cancer Research, Vol. 74, No. 21, 01.11.2014, p. 5955-5962.

Research output: Contribution to journalArticle

De Carvalho Barbosa, M, Kosturakis, AK, Eng, C, Wendelschafer-Crabb, G, Kennedy, WR, Simone, DA, Wang, XS, Cleeland, CS & Dougherty, PM 2014, 'A quantitative sensory analysis of peripheral neuropathy in colorectal cancer and its exacerbation by oxaliplatin chemotherapy', Cancer Research, vol. 74, no. 21, pp. 5955-5962. https://doi.org/10.1158/0008-5472.CAN-14-2060
De Carvalho Barbosa, Mariana ; Kosturakis, Alyssa K. ; Eng, Cathy ; Wendelschafer-Crabb, Gwen ; Kennedy, William R ; Simone, Donald A ; Wang, Xin S. ; Cleeland, Charles S. ; Dougherty, Patrick M. / A quantitative sensory analysis of peripheral neuropathy in colorectal cancer and its exacerbation by oxaliplatin chemotherapy. In: Cancer Research. 2014 ; Vol. 74, No. 21. pp. 5955-5962.
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