theanine and Colorectal-Neoplasms

Capecitabine-based adjuvant chemotherapy for colorectal cancer patients often causes adverse events (AEs), such as diarrhea, stomatitis, anorexia, and hand-foot syndrome (HFS). Cystine and theanine were reported to attenuate some chemotherapy-associated AEs, and hence are also expected to attenuate capecitabine-induced AEs. Therefore, we aimed to investigate the safety and efficacy of cystine/theanine treatment in colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery.. A total of 100 colorectal cancer patients treated with capecitabine as an adjuvant chemotherapy after surgery were randomly allocated into the cystine/theanine group (n = 52) or the placebo group (n = 48). The primary endpoint was incidence rate of diarrhea of grade 1 or higher in accordance with the Common Terminology Criteria for AEs (CTCAE) v.4.0, Japanese Clinical Oncology Group (JCOG) version. The secondary endpoints included incidence rates of other AEs (CTCAE v.4.0-JCOG), as well as the incidence rate of HFS according to the HFS grading scale.. There were no significant differences in capecitabine-induced AEs between the two groups. However, the incidence rate of diarrhea of grade 1 or higher tended to be lower in the cystine/theanine group than the placebo group (18.4% vs. 28.9%, p = 0.169) as well as the incidence rate of HFS of grade 1 or higher (CTCAE v.4.0-JCOG or HFS grading scale) (67.4% vs. 77.8%, p = 0.185, 67.3% vs. 80.0%, p = 0.124, respectively).. This trial demonstrated that cystine/theanine treatment of colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery is safe and has the tendency to reduce the incidence rate of diarrhea or HFS.. UMIN000024784.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Colorectal Neoplasms; Cystine; Diarrhea; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Glutamates; Hand-Foot Syndrome; Humans; Male; Middle Aged; Stomatitis

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

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Cystine; Female; Fluorouracil; Glutamates; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peripheral Nervous System Diseases; Pilot Projects; Quality of Life

Although adjuvant capecitabine therapy for patients with colorectal cancer after surgery often causes adverse events (AEs), such as diarrhoea, stomatitis, anorexia and hand-foot syndrome (HFS), there are no standard prevention therapies. Cystine and theanine were reported to attenuate some chemotherapy-associated AEs, and are also expected to attenuate the AEs caused by capecitabine treatment. Therefore, our present study aimed to determine the safety and efficacy of cystine/theanine therapy in patients with colorectal cancer undergoing capecitabine-based adjuvant chemotherapy after surgery.. A multi-institutional, prospective, randomised, double-blinded, placebo-controlled, phase II trial is being planned. Patients with colorectal cancer treated with capecitabine as an adjuvant chemotherapy will be randomised into either the cystine/theanine group (n=50) or placebo group (n=50). Data will be collected during four courses of capecitabine therapy. The primary endpoint will be incidence rate of diarrhoea of grade 1 or higher in accordance with the Common Terminology Criteria for AEs (CTCAE) v.4.0, Japanese Clinical Oncology Group (JCOG) version. The secondary endpoints are incidence rates of other AEs (CTCAE v.4.0-JCOG), scores of the Japanese version of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire module for all patients with cancer (QLQ-C30) and for patients with colorectal cancer (QLQ-CR29), incidence rate of HFS according to the HFS grading scale, protocol adherence, completion rate of four courses of capecitabine therapy and the proportion of completion without delay or dose reduction, time to completion of four courses of capecitabine and total dose of capecitabine. A sample size of 100 patients will be analysed between November 2016 and April 2018.. Ethical approval was obtained at all participating institutions. The results of this study will be submitted for publication in international peer-reviewed journals.. UMIN000024784; Pre-results.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Capecitabine; Chemotherapy, Adjuvant; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Cystine; Disease-Free Survival; Double-Blind Method; Female; Glutamates; Humans; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Treatment Outcome

Colorectal cancer is considered as a major cancer among all types of cancers, especially in developed countries. The colorectal cancer has few to no symptoms and mostly the tumor is often diagnosed in the later stage of cancer. Oxidative stress and inflammatory reaction play an important role in the expansion and the progression of colorectal cancer. Theanine exhibits antioxidant and anti-inflammatory potential against various diseases. As a result of its antioxidant and anti-inflammatory nature, in this study, we estimated the protective effect of theanine against 1,2-dimethylhydrazine (DMH)-induced colorectal cancer and explored the possible mechanism. Subcutaneous injection (35 mg/kg) of DMH was used to induce colorectal cancer in rats. Rats were divided into different groups and were orally administrated with theanine (5, 10, and 20 mg/kg) for 16 weeks. Body weight, tumor size, and average tumor weight were determined at the end of the experimental study. Biochemical tests, antioxidant properties, phase I and phase II enzymes, and inflammatory mediators were estimated. The mRNA expression of p38 mitogen-activated protein kinase (p38MAPK), p53, and apoptosis was also estimated at the end of the experimental study. Theanine significantly (p < .001) increases the body weight and suppressed the average tumor size in DMH-induced colorectal cancer. Similarly, it significantly (p < .001) reduces the level of prostaglandin (PGE

Topics: 1,2-Dimethylhydrazine; Animals; Anti-Inflammatory Agents; Antioxidants; Colorectal Neoplasms; Dose-Response Relationship, Drug; Glutamates; Oxidative Stress; Rats