Protective effect of the oral administration of cystine and theanine on oxaliplatin-induced peripheral neuropathy: a pilot randomized trial

Int J Clin Oncol. 2020 Oct;25(10):1814-1821. doi: 10.1007/s10147-020-01728-4. Epub 2020 Jun 27.

Abstract

Background: Oxaliplatin, one of the key cytotoxic drugs for colorectal cancer, frequently causes peripheral neuropathy which leads to dose modification and decreased patients' quality of life. However, prophylactic or therapeutic measures have not yet been established. Orally administered amino acids, cystine and theanine, promoted the synthesis of glutathione which was one of the potential candidates for preventing the neuropathy. The aim of this study was to determine whether daily oral administration of cystine and theanine attenuated oxaliplatin-induced peripheral neuropathy (OXLIPN).

Methods: Twenty-eight colorectal cancer patients who received infusional 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) therapy were randomly and evenly assigned to the cystine and theanine group and the control group. OXLIPN was assessed up to the sixth course using original 7-item questionnaire as well as Common Terminology Criteria for Adverse Events (CTCAE) grading scale.

Results: Neuropathy scores according to our original questionnaire were significantly smaller in the cystine and theanine group at the fourth (p = 0.026), fifth (p = 0.029), and sixth course (p = 0.038). Furthermore, significant differences were also observed in CTCAE neuropathy grades at the fourth (p = 0.037) and the sixth course (p = 0.017). There was one patient in each group who required dose reduction due to OXLIPN. Except for neurotoxicity, no significant differences were noted in the incidence of adverse events, and the total amount of administered oxaliplatin.

Conclusion: The results demonstrated the daily oral administration of cystine and theanine attenuated OXLIPN.

Keywords: Amino acid; CIPN; Colorectal cancer; Cystine; Neuropathy; Oxaliplatin; Theanine.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Colorectal Neoplasms / drug therapy*
  • Cystine / administration & dosage
  • Female
  • Fluorouracil / adverse effects
  • Glutamates / administration & dosage*
  • Humans
  • Leucovorin / adverse effects
  • Male
  • Middle Aged
  • Organoplatinum Compounds / adverse effects
  • Oxaliplatin / administration & dosage
  • Oxaliplatin / adverse effects*
  • Peripheral Nervous System Diseases / chemically induced*
  • Peripheral Nervous System Diseases / prevention & control*
  • Pilot Projects
  • Quality of Life

Substances

  • Glutamates
  • Organoplatinum Compounds
  • Oxaliplatin
  • Cystine
  • theanine
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol