Oral administration of the amino acids cystine and theanine attenuates the adverse events of S-1 adjuvant chemotherapy in gastrointestinal cancer patients.
BACKGROUND
Nutritional therapy is used to reduce the adverse events (AEs) of anticancer drugs. Here, we determined whether the amino acids cystine and theanine, which provide substrates for glutathione, attenuated the AEs of S-1 adjuvant chemotherapy.


METHODS
Patients scheduled to receive S-1 adjuvant chemotherapy were randomized to the C/T or the control groups. The C/T group received 700 mg cystine and 280 mg theanine orally 1 week before the administration of S-1, which then continued for 5 weeks. Each group received S-1 for 4 weeks. Blood sampling was performed and AEs were evaluated (CTCAE ver. 4.0) before and after the administration of S-1. S-1 was discontinued when AEs ≥ grade 2 occurred.


RESULTS
The incidences of AEs of any grade and those over grade 2 were lower in the C/T group than in the controls. The incidence of diarrhea (G ≥ 2) was significantly less (p < 0.05) in the C/T group (3.1 %) than in the controls (25.8 %). The duration and completion rate of the S-1 adjuvant chemotherapy were significantly longer (p < 0.01) and higher (p < 0.01), respectively, in the C/T group (complete ratio: 75.0 %, duration: 24.8 ± 5.8 days) than in the controls (complete ratio: 35.5 %, duration: 20.0 ± 7.7 days).


CONCLUSIONS
The oral administration of cystine and theanine attenuated the AEs of S-1 adjuvant chemotherapy and increased the S-1 completion rate, suggesting that cystine and theanine is a useful supportive care for chemotherapy.
Department of Surgery, Sendai City Medical Center, 5-22-1 Tsurugaya, Miyagino-ku, Sendai, Miyagi, 983-0824, Japan. tsuchiya@openhp.or.jp.
Takashi
T
Tsuchiya
Department of Surgery, Sendai City Medical Center, 5-22-1 Tsurugaya, Miyagino-ku, Sendai, Miyagi, 983-0824, Japan.
Hiroshi
H
Honda
Department of Surgery, Sendai City Medical Center, 5-22-1 Tsurugaya, Miyagino-ku, Sendai, Miyagi, 983-0824, Japan.
Masaya
M
Oikawa
Department of Surgery, Sendai City Medical Center, 5-22-1 Tsurugaya, Miyagino-ku, Sendai, Miyagi, 983-0824, Japan.
Tetsuya
T
Kakita
Department of Surgery, Sendai City Medical Center, 5-22-1 Tsurugaya, Miyagino-ku, Sendai, Miyagi, 983-0824, Japan.
Atsushi
A
Oyama
Department of Surgery, Sendai City Medical Center, 5-22-1 Tsurugaya, Miyagino-ku, Sendai, Miyagi, 983-0824, Japan.
Hidekazu
H
Oishi
Department of Pharmacy, Sendai City Medical Center, Sendai, Japan.
Katsuyuki
K
Tochikubo
Department of Pharmacy, Sendai City Medical Center, Sendai, Japan.
Takanao
T
Hashimoto
Institute for Innovation, Ajinomoto Co., Inc., Kanagawa, Japan.
Shigekazu
S
Kurihara
Institute for Innovation, Ajinomoto Co., Inc., Kanagawa, Japan.
Tetsuro
T
Shibakusa
Wellness Business Division, Ajinomoto Co., Inc., Tokyo, Japan.
Takashi
T
Kayahara
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D003553:Cystine / Q000008:administration & dosage*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D016903:Drug Monitoring; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology / Q000378:metabolism; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000473:pathology; D005971:Glutamates / Q000008:administration & dosage*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D020011:Protective Agents / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D005971:Glutamates; D020011:Protective Agents; C079198:S 1 (combination); D005641:Tegafur; D003553:Cystine; D010094:Oxonic Acid; C026166:theanine; D005978:Glutathione
Adverse events; Chemotherapy; Cystine/theanine; S-1; Supportive care