Purpose Oxaliplatin-induced peripheral neurotoxicity (OPN) is frequent and potentially severe, but successful treatment of this condition is still an unmet clinical need. We aimed to determine whether treatment with goshajinkigan (TJ-107), a traditional Japanese medicine, is better than placebo in preventing OPN in patients with advanced or recurrent colorectal cancer patients treated with standard FOLFOX regimens. Methods In this phase 2, randomized, double-blind, placebo-controlled study, patients undergoing oxaliplatin-based chemotherapy were randomized to receive either oral TJ-107 (7.5 g) or matching placebo daily. The severity of OPN was assessed according to the Common Toxicity Criteria for Adverse Events at baseline, every 2 weeks until the 8th cycle, and every 4 weeks thereafter until the 26th week. The primary endpoint was the incidence of grade 2 or greater OPN until the 8th cycle of chemotherapy. Results Analyses were done by intention to treat. Eighty-nine patients were randomly assigned to receive either TJ-107 ( n = 44) or placebo ( n = 45) between May 2009 and March 2010. The incidence of grade 2 or greater OPN until the 8th cycle was 39 and 51 % in the TJ-107 and placebo groups, respectively (relative risk (RR), 0.76; 95 % CI, 0.47–1.21). The incidence of grade 3 OPN was 7 % (TJ-107) vs. 13 % (placebo) (0.51, 0.14–1.92). No concerns regarding toxicity emerged with TJ-107 treatment. Conclusions TJ-107 appears to have an acceptable safety margin and a promising effect in delaying the onset of grade 2 or greater OPN without impairing FOLFOX efficacy.

Background Cancer cachexia is characterized by weight loss and is associated with increased morbidity and mortality in patients with cancer. Anamorelin (ONO‐7643; ANAM) is a novel and selective ghrelin receptor agonist that improves appetite, lean body mass (LBM), body weight, and anorexia. Methods This multicenter, open‐label, single‐arm study investigated the efficacy and safety of 100 mg anamorelin in 50 Japanese patients with advanced and unresectable gastrointestinal (colorectal, gastric, or pancreatic) cancer. ANAM was administered once daily over 12 weeks. The primary endpoint was the proportion of patients that maintained or gained LBM over the course of the study. Secondary endpoints included changes in LBM, body weight, quality of life (QoL), and nutritional status biomarkers. Results The proportion of patients who responded to treatment was 63.3% (95% CI, 48.3%‐76.6%), with a least square mean ± SE change in LBM and body weight from baseline of 1.89 ± 0.36 kg and 1.41 ± 0.61 kg, respectively. Appetite‐related questions on the QoL questionnaire showed that ANAM improved appetite. Adverse events occurred in 79.6% of patients, and the most common treatment‐related adverse events were increased γ‐glutamyl transpeptidase (8.2%), diabetes mellitus (6.1%), hyperglycemia (6.1%), and prolonged QRS complex (6.1%). Conclusions ANAM improved anorexia and patients' nutritional status, resulting in rapid increases in LBM and body weight in patients with advanced gastrointestinal cancer who had cancer cachexia. ANAM treatment was well tolerated over 12 weeks. ANAM is a potential clinically beneficial pharmacotherapeutic option for patients with advanced gastrointestinal cancer who have cancer cachexia.

IMPORTANCE Oxaliplatin-based chemotherapy is associated with debilitating peripheral sensory neuropathy (PSN) for patients with stage III colon cancer. OBJECTIVE To assess disease-free survival (DFS) and long-lasting PSN in patients treated with 3 vs 6 months of adjuvant oxaliplatin-based chemotherapy. DESIGN, SETTING, AND PARTICIPANTS An open-label, multicenter, phase 3 randomized clinical trial of 1313 Asian patients with stage III colon cancer was conducted investigating the noninferiority of 3 vs 6 months of adjuvant oxaliplatin-based chemotherapy. From August 1, 2012, to June 30, 2014, participants were randomized to the 2 treatment groups. Data were analyzed from July 2017 to June 2018. INTERVENTIONS Patients were randomized to receive 3 or 6 months of adjuvant chemotherapy. The choice of chemotherapy regimen, with the drugs modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine plus oxaliplatin (CAPOX), was at the discretion of the treating physician. MAIN OUTCOMES AND MEASURES The primary outcome was DFS. Secondary end points included the evaluation of PSN for up to 3 years and overall survival. RESULTS Of the 1313 patients (651 were women and mean age was 66 [range, 28-85] years) enrolled and randomized, 22 were not treated because 10 were unable to begin treatment within 2 weeks of enrollment, 7 withdrew their consent, and 5 were not treated for various other reasons. Of 1291 patients treated (650 in the 3-month arm and 641 in the 6-month arm), 969 (75%) received the chemotherapy drug CAPOX. The hazard ratio (HR) for DFS of the 3-month arm compared with the 6-month arm was 0.95 (95% CI, 0.76-1.20). Hazard ratios were 1.07 (95% CI, 0.71-1.60) and 0.90 (95% CI, 0.68-1.20) for the drugs mFOLFOX6 and CAPOX, and 0.81 (95% CI, 0.53-1.24) and 1.07 (95% CI, 0.81-1.40) for patients with low-risk disease (TNM classification stages T1-3 and N1) and high-risk disease (stages T4 or N2), respectively. The rates of any grade of PSN lasting for 3 years in the 3-month vs 6-month treatment arms were 9.7% vs 24.3% (P < .001). Incidence of PSN lasting for 3 years was significantly lower for patients treated with CAPOX than for patients treated with mFOLFOX6 in both the 3-month (7.9% vs 15.7%; P = .04) and 6-month arms (21.0% vs 34.1%; P = .02). CONCLUSIONS AND RELEVANCE The incidence of long-lasting PSN was significantly lower for 3 months than for 6 months of therapy, and significantly lower for treatment with the drug CAPOX than with mFOLFOX6. Since the shortened therapy duration did not compromise outcomes, a 3-month course of CAPOX may be the most appropriate treatment option, particularly for patients with low-risk disease. TRIAL REGISTRATION UMIN Clinical Trials Registry: UMIN000008543

Purpose Hangeshashinto (TJ-14, a Kampo medicine), which reduces the level of prostaglandin E2 and affects the cyclooxygenase activity, alleviates chemotherapy-induced oral mucositis (COM). We conducted a double-blind, placebo-controlled, randomized comparative trial to investigate whether TJ-14 prevents and controls COM in patients with colorectal cancer.MethodsNinety-three patients with colorectal cancer who developed moderate-to-severe COM (WHO grade ≧1) during any cycle of chemotherapy using FOLFOX, FOLFIRI, and/or XELOX treatment were randomly assigned to receive either TJ-14 (n = 46) or placebo (n = 47). Patients received the administration of placebo or TJ-14 for 2 weeks at the start of the next course of chemotherapy. Patients were assessed three times per week for safety and for COM incidence and its severity using the WHO grading. ResultsNinety eligible patients (TJ-14; 43, placebo; 47) per protocol set analysis were included in the analysis after the key-opening. Although the incidence of grade ≧2 oral mucositis was lower for patients treated with TJ-14 compared to those treated with placebo, there was no significant difference (48.8 vs. 57.4 %; p = 0.41). The median duration of grade ≧2 mucositis was 5.5 versus 10.5 days (p = 0.018). No difference in other treatment toxicity was observed between the two groups, and patients exhibited high compliance in dosing administration.ConclusionThe present study results did not meet the primary endpoint. However, TJ-14 demonstrated a significant effect in the treatment of grade ≧2 mucositis in patients with colorectal cancer compared to the placebo.

Background The characterisation of desmoplastic reaction (DR) has emerged as a new, independent prognostic determinant in colorectal cancer. Herein, we report the validation of its prognostic value in a randomised controlled study (SACURA trial). Methods The study included 991 stage II colon cancer patients. DR was classified by the central review as Mature, Intermediate or Immature based on the presence of hyalinised collagen bundles and myxoid stroma at the desmoplastic front. All clinical and pathological data, including DR characterisations, were prospectively recorded and analysed 5 years after the completion of the registration. Results The five-year relapse-free survival (RFS) rate was the highest in the Mature group (N = 638), followed by the Intermediate (N = 294) and Immature groups (N = 59). Multivariate analysis revealed that DR classification was an independent prognostic factor, and based on Harrell’s C-index, the Cox model for predicting RFS was significantly improved by including DR. In the conditional inference tree analysis, DR categorisation was the first split factor for predicting RFS, followed by T-stage, microsatellite instability status and budding. Conclusions Histological categorisation of DR provides important prognostic information that could contribute to the efficient selection of stage II colon cancer patients who would benefit from postoperative adjuvant therapy.