J Clin Neurol.  2018 Jan;14(1):81-89. 10.3988/jcn.2018.14.1.81.

A Prospective Study of Chronic Oxaliplatin-Induced Neuropathy in Patients with Colon Cancer: Long-Term Outcomes and Predictors of Severe Oxaliplatin-Induced Neuropathy

• Kim SH
• Kim W
• Kim JH
• Woo MK
• Baek JY
• Kim SY
• Chung SH
• Kim HJ

• KMID: 2399603
• DOI: http://doi.org/10.3988/jcn.2018.14.1.81

Abstract

BACKGROUND AND PURPOSE
The objective of this study was to determine the incidence and long-term outcomes of oxaliplatin-induced peripheral neuropathy (OIPN), as well as predictors of its severe form.
METHODS
Sixty-nine patients who were taking oxaliplatin for colon cancer were prospectively followed prior to starting chemotherapy and after 4, 8, and 12 cycles of chemotherapy. Thirty-six patients completed the follow-up at 1 year after the end of chemotherapy. The patients were assessed using clinical assessment scales and nerve conduction studies (NCS) at each follow-up visit.
RESULTS
By applying the National Cancer Institute Common Toxicity criteria, OIPN was classified as grade 1 in 30 (44%) patients, grade 2 in 25 (36%), and grade 3 in 10 (14%) at the completion of therapy. At 1 year after the treatment, OIPN of grades 1, 2, and 3 was found in 50, 3, and 11% of the patients, respectively. Multivariate analysis showed that reductions of the amplitude of the sensory action potential of >11.5% in the median nerve between baseline and four cycles of chemotherapy (odds ratio=5.603, p=0.031) and of >22.5% in the sural nerve between four and eight cycles of chemotherapy (odds ratio=5.603, p=0.031) were independently associated with the risk of developing grade-3 OIPN.
CONCLUSIONS
While the severity of OIPN can improve after oxaliplatin discontinuation, more than half of the patients in this study still had OIPN at 1 year after discontinuation. Early changes in the NCS results for sensory nerves can predict the development of severe OIPN during treatment.

Keyword

oxaliplatin; oxaliplatin-induced peripheral neuropathy; colon cancer; predictor

MeSH Terms

Action Potentials
Colon*
Colonic Neoplasms*
Drug Therapy
Follow-Up Studies
Humans
Incidence
Median Nerve
Multivariate Analysis
National Cancer Institute (U.S.)
Neural Conduction
Peripheral Nervous System Diseases
Prospective Studies*
Sural Nerve
Weights and Measures

Figure

• 

  Fig. 1 Proportion of patients with peripheral sensory neuropathy of grades 1, 2, and 3 who were treated with FOLFOX (oxaliplatin plus fluorouracil and leucovorin). (A) During treatment (n=69) and (B) after a 1-year follow-up (n=36). NCI-CTCv3: version 3.0 of the National Cancer Institute common toxicity criteria.

• 

  Fig. 2 Scores on the EORTC QLQ-CIPN20 during treatment. (A) Sensory, motor, and autonomic scores, and (B) sensory subscale scores. Higher values indicate more-severe symptoms. Data are mean and standard error values. EORTC QLQ-CIPN20: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 module.

• 

  Fig. 3 Scores on EORTC QLQ-CIPN20 during treatment and after 6-month and 1-year follow-ups. (A) sensory, motor, and autonomic scores, (B) sensory scores according to NCI-CTCv3 grade, (C) motor scores according to NCI-CTCv3 grade, and (D) autonomic scores according to NCI-CTCv3 grade. Data are mean and standard error values. EORTC QLQ-CIPN20: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 module, NCI-CTCv3: version 3.0 of the National Cancer Institute common toxicity criteria.

• 

  Fig. 4 a-SAP (A) and SCV (B) in the median, ulnar, and sural nerves during treatment and after 6-month and 1-year follow-ups. Data are mean and standard error values. a-SAP: amplitude of the sensory nerve action potential, SCV: sensory conduction velocity.

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