Protective effect of the oral administration of cystine and theanine on oxaliplatin-induced peripheral neuropathy: a pil
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ORIGINAL ARTICLE
Protective effect of the oral administration of cystine and theanine on oxaliplatin‑induced peripheral neuropathy: a pilot randomized trial Minoru Kobayashi1,2 · Ryuichiro Sato1 · Toshihiro Komura3 · Hidetaka Ichikawa2 · Tomoaki Hirashima2 · Satoshi Otake1 · Naoya Akazawa1 · Takashi Yazawa1 · Tomoya Abe1 · Takaho Okada1 · Tetsuya Kakita1 · Masaya Oikawa1 · Takashi Tsuchiya1 Received: 16 February 2020 / Accepted: 15 June 2020 © The Author(s) 2020
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 Colorectal cancer · Neuropathy · Oxaliplatin · CIPN · Amino acid · Cystine · Theanine
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10147-020-01728-4) contains supplementary material, which is available to authorized users. * Takashi Tsuchiya [email protected] 1
Department of Surgery, Sendai City Medical Center, 5‑22‑1 Tsurugaya, Miyagino‑ku, Sendai, Miyagi 983‑0824, Japan
2
Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
3
Department of Surgery, Omagari Kousei Medical Center, Akita, Akita, Japan
Colorectal cancer (CRC) is one of the most common cancers in the world. In 2018, an estimated 1,800,000 cases were newly diagnosed and nearly 860,000 patients died of the disease [1]. Surgical resection is the only curative treatment of localized CRC, and advanced disease is oft
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