Oral administration of the amino acids cystine and theanine attenuates the adverse events of S-1 adjuvant chemotherapy in gastrointestinal cancer patients

Abstract

BackgroundNutritional 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.MethodsPatients 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.ResultsThe 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).ConclusionsThe 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.

Efficacy of oral administration of cystine and theanine in patients with colorectal cancer undergoing capecitabine-based adjuvant chemotherapy after surgery: study protocol for a multi-institutional, randomised, double-blinded, placebo-controlled, phase II trial

“…Previous research has shown that oral administration of cystine/theanine attenuates the AEs of S-1 adjuvant chemotherapy in patients with colorectal cancer after surgery. 11 The incidence rate of diarrhoea was significantly less in the cystine/theanine group (4.5%) than in the control group (41.7%). The completion rate of the first course of S-1 adjuvant chemotherapy at the prescribed dose was significantly higher in the cystine/theanine group (90.9%) than in the control group (41.7%).…”

Efficacy of oral administration of cystine and theanine in colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery: a multi-institutional, randomized, double-blinded, placebo-controlled, phase II trial (JORTC-CAM03)

“…Sample size calculations were made based on a previous study [10]. The incidence rate of diarrhea induced by adjuvant S-1 therapy in colorectal cancer patients after surgery was significantly less in the cystine/theanine group (4.5%) than in the control group (41.7%).…”

“…We acknowledge that this study has several limitations. First, the sample size calculation was based on a previous study on the effects of cystine/theanine on S-1-induced diarrhea [10], because we had no data of the effects of cystine/ theanine on capecitabine-induced AEs. Therefore, although capecitabine is an oral pyrimidine fluoride anticancer drug similar to S-1, and the incidence rate of diarrhea after capecitabine monotherapy is also close to that after S-1 monotherapy, our results should be interpreted with caution.…”

“…It was also reported that perioperative oral administration of cystine/ theanine suppressed inflammation and enhanced recovery after surgery [9]. Moreover, previous research demonstrated that the incidence rate of diarrhea induced by S-1 adjuvant chemotherapy in colorectal cancer patients after surgery was significantly less in the cystine/theanine group (4.5%) than in the control group (41.7%) [10]. It was also demonstrated that the completion rate of the first course of S-1 at the prescribed dose was significantly higher in the cystine/theanine group (90.9%) than in the control group (41.7%).…”

Role of nutrition in gastroenterological surgery

“…Oral administration of cystine and theanine during the perioperative period reportedly lowered postoperative plasma interleukin‐6 levels, C‐reactive protein levels, PMN counts and body temperature in cancer patients undergoing distal gastrectomy. Moreover, this combination has been demonstrated to attenuate adverse events of S‐1 adjuvant chemotherapy in GI cancer patients . A possible mechanism might involve enhancement of glutathione metabolism by cystine and theanine …”