Oxaliplatinassociated neuropathy

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Reducing oxaliplatin-associated sensory
neurotoxicity
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Glutamine

• Neutral gluconeogenic non-essential a.a.
• stored primarily in skeletal muscle liver
  (60 free a.a. pool).
• Primary carrier of nitrogen between
• tissues main energy source for rapidly
• proliferating cells (enterocytes, lymphocytes,
  fibroblasts).
• A precursor for glutathione (GSH)
• Glutamine is depleted in stress states
• (e.g. major surgery, sepsis, cancer).
• Clin Cancer Res. 2001
  May7(5)1192-7

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Glutamine is an important fuel for rapidly
dividing cells
A conditional essential a.a.
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Glutamine supplements is essential for cancer
patients

• Support host
• Restore host glutathione (GSH)
• Prevent or repair damage to bowel
• Ameliorate side effects
• Neuropathy, mucositis, enteritis
• Maintain immune function (BMT)
• Enhance NK cell activity

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Clinical trials using glutamine in preventing
toxicity from chemotherapy
Clinical Cancer Res 2001 1192-7
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Oral glutamine is effective for preventing
oxaliplatin-induced neuropathy in CRC patients
Wang WS, et al. 2006
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Oral glutamine is effective for preventing
oxaliplatin-induced neuropathy in CRC patients
Wang WS, et al. 2006
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Oral glutamine is effective for preventing
oxaliplatin-induced neuropathy in CRC patients
Wang WS, et al. 2006
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Oral glutamine is effective for preventing
oxaliplatin-induced neuropathy in CRC patients

• Glutamine does not support tumor growth.
• Enhances natural killer cell activity decreases
  tumor growth in a xenograft model, and combined
  with chemotherapy or radiation therapy it
  enhances tumor kill.

Wang WS, et al. 2006
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Oral glutamine is effective for preventing
oxaliplatin-induced neuropathy in CRC patients
Wang WS, et al. 2006