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

Abstract

IntroductionAlthough 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.Methods and analysisA 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.Ethics and disseminationEthical approval was obtained at all participating institutions. The results of this study will be submitted for publication in international peer-reviewed journals.Trial registration numberUMIN000024784; Pre-results.

Anlotinib Monotherapy for Refractory Metastatic Colorectal Cancer: A Double-Blinded, Placebo-Controlled, Randomized Phase III Trial (ALTER0703)

“…The QLQ-C30 ranges from 0 to 100, when 100 represents highest level of functioning and best health-related QoL. At least 10 points of change on the QLQ-C30 scale is considered to be clinically meaningful [16,18]. EQ-5D questionnaires were to evaluate performance status on mobility, self-care, usual activities, pain/discomfort, anxiety/depression and visual analogue scale.…”

“…Patient‐reported QoL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire‐Core 30 (QLQ‐C30) [16] and EuroQol‐5 dimension (EQ‐5D) at every visit before any study‐related procedures were conducted [17]. The QLQ‐C30 questionnaires involved five items of functional status (physical, role, emotional, cognitive, and social function), eight items of symptom status (fatigue, pain, nausea, dyspnea, isomnia, appetite loss, constipation, and diarrhea), health status, and financial difficult.…”

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)

“…Capecitabine is an oral pyrimidine fluoride anticancer drug similar to S-1, and the incidence rate of diarrhea after capecitabine monotherapy according to the prescribing information is 36.8% [6]. Therefore, it was estimated that the incidence rate of diarrhea after capecitabine therapy would be 5% with cystine/theanine and 25% with placebo [11]. Assuming a 10% dropout rate, we calculated 50 patients for each group (100 samples in total) with a onesided significance level of 5% and a power of 80%.…”

“…The design and rationale of this trial have been published previously [11]. This trial was a multi-institutional, randomized, double-blinded, placebo-controlled, phase II trial investigating the safety and efficacy of oral administration of cystine/theanine in colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery.…”

“…AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0, Japanese Clinical Oncology Group (JCOG) version. HFS was also assessed by the HFS grading scale suggested by Blum JL, et al (Supplemental Table 1) [11,13]. Health-associated quality of life was assessed according to the Japanese version of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire module for all cancer patients (QLQ-C30) and for colorectal cancer patients (QLQ-CR29).…”