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Background: Long‐term anti‐EGFR antibody treatment increases the risk of severe dermatologic toxicities. This single‐arm, phase II trial aimed to investigate the strategy of switching from cetuximab to bevacizumab in combination with FOLFIRI based on early tumor shrinkage (ETS) in patients with RAS wild‐type metastatic colorectal cancer (mCRC). Methods: Radiologic assessment was performed to evaluate ETS, defined as ≥20% reduction in the sum of the largest diameters of target lesions 8 weeks after the introduction of FOLFIRI plus cetuximab. ETS‐negative patients switched to FOLFIRI plus bevacizumab, whereas ETS‐positive patients continued FOLFIRI plus cetuximab for eight more weeks, with a switch to FOLFIRI plus bevacizumab thereafter. The primary endpoint was progression‐free survival. Results: This trial was prematurely terminated due to poor accrual after a total enrollment of 30 patients. In 29 eligible patients, 7 were ETS‐negative and 22 were ETS‐positive. Two ETS‐negative patients and 17 ETS‐positive patients switched to FOLFIRI plus bevacizumab 8 weeks and 16 weeks after initial FOLFIRI plus cetuximab, respectively. Median progression‐free and overall survival durations were 13.4 and 34.7 months, respectively. Six (20%) patients experienced grade ≥3 paronychia, which improved to grade ≤2 by 18 weeks. Grade ≥3 acneiform rash, dry skin, and pruritus were not observed in any patients. Conclusions: Our novel treatment strategy delivered acceptable survival outcomes and reduced severe dermatologic toxicities. [ABSTRACT FROM AUTHOR]

Background: Cancer cachexia is a syndrome characterized by anorexia and decreased body weight. This study evaluated the efficacy and safety of anamorelin, an orally active, selective ghrelin receptor agonist, in patients with cancer cachexia and a low body mass index (BMI). Methods: This multicenter, open‐label, single‐arm study enrolled Japanese patients with non–small cell lung cancer or gastrointestinal cancer with cancer cachexia (BMI < 20 kg/m2, involuntary weight loss > 2% in the last 6 months, and anorexia). Patients were administered 100 mg of anamorelin once daily for up to 24 weeks. The primary end point was a composite clinical response (CCR) at 9 weeks, which was defined as an increase in body weight of ≥5% from the baseline, an increase of ≥2 points in the score of the 5‐item Anorexia Symptom Scale of the Functional Assessment of Anorexia/Cachexia Therapy, and being alive. Results: One hundred two patients were eligible and enrolled. The means and standard deviations for age and BMI were 71.0 ± 8.2 years and 17.47 ± 1.48 kg/m2, respectively. The CCR rate at 9 weeks was 25.9% (95% confidence interval [CI], 18.3%‐35.3%), which met the primary end point with a lower 95% CI exceeding the prespecified minimum of 8%. Improvements in body weight and anorexia were durable and were accompanied by improvements in patients' global impression of change for appetite/eating‐related symptoms and overall condition. Adverse drug reactions occurred in 37 of 101 treated patients (36.6%), with the most common being glycosylated hemoglobin increases, constipation, and peripheral edema. Conclusions: Anamorelin improved body weight and anorexia‐related symptoms in patients with cancer cachexia and a low BMI with durable efficacy and favorable safety and tolerability. Lay Summary: Anamorelin is a drug that stimulates appetite and promotes weight gain.This clinical trial was aimed at determining its efficacy and safety in Japanese cancer patients with a low body mass index and cachexia, a syndrome associated with anorexia and weight loss.Anamorelin was found to improve body weight and anorexia‐related symptoms in these patients, and these effects were durable for up to 24 weeks. Moreover, anamorelin was generally well tolerated.These findings suggest that anamorelin is a valuable treatment option for patients with cancer cachexia and a low body mass index. This single‐arm trial is aimed at investigating the efficacy and safety of anamorelin in Japanese patients with cancer cachexia and a low body mass index. Anamorelin improves body weight and anorexia‐related symptoms with durable efficacy and favorable safety and tolerability. [ABSTRACT FROM AUTHOR]

Background: Oxaliplatin is a key drug for the chemotherapy of colorectal cancer; however, it is also known to cause non‐cirrhotic portal hypertension. We aimed to identify the characteristics of patients who developed esophagogastric varices (EGVs) after treatment with oxaliplatin. Methods: This study retrospectively analyzed patients with colorectal cancer who were treated with chemotherapy including oxaliplatin between 2010 and 2016. All patients were evaluated by contrast‐enhanced computed tomography (CE‐CT) every 3 months both during and after treatment; and endoscopy was performed when appearance of portal hypertension was suspected. Results: A total of 106 patients were divided into two groups: EGV formation (n = 6) and EGV non‐formation (n = 100). In the EGV group, platelet counts decreased and the size of the spleen calculated by CT (CT spleen index; CT‐SI) increased markedly. The highest area under the receiver operating characteristic curve (AUC) for the change in platelet counts was 0.81 (80% sensitivity and 83% specificity) at 3 months post treatment, and the maximum AUC for CT‐SI was 0.89 (79% sensitivity and 83% specificity) at 6 months post treatment. Conclusions: EGV formation could be predicted by the assessment of platelet counts and spleen size. If progressive splenomegaly and thrombocytopenia are observed not only during but also after completion of the oxaliplatin‐containing chemotherapy, EGVs should be confirmed by endoscopy for avoiding subsequent rupture. [ABSTRACT FROM AUTHOR]

In patients with impaired renal function, S‐1–related toxicities increase due to higher exposure of 5‐fluorouracil (5‐FU). Our previous pharmacokinetic study in 16 cancer patients with various renal functions developed an S‐1 dosage formula based on individual creatinine clearance (CLcr) and body surface area (BSA). To evaluate and refine the formula, this prospective study was conducted. Thirty‐three patients with various renal functions received S‐1 for 4 weeks at doses determined by the nomogram derived from the previously developed formula. A series of blood samples were collected after the first dose to calculate the area under the concentration‐time curve (AUC) of 5‐FU. Thirty patients with BSA of 1.14‐1.84 m2 and CLcr of 23.8‐96.4 mL/min were assessable for pharmacokinetics. The observed daily AUC ranged from 712.6 to 2868.7 ng·h/mL, and 18 patients achieved the target AUC (1447.8 ± 545.4 ng·h/mL). Three patients experienced S‐1–related grade 3 adverse events during the first course. In the population pharmacokinetic analysis from the combined data of 46 patients in this study and the previous study, sex was identified as a statistically significant covariate for 5‐FU clearance. Hence, the refined formula includes sex as an additional factor: Recommended daily dose = target AUC × (14.5 + 8.23 × SEX [0 for female and 1 for male] + 0.301 × CLcr) × BSA. Revised nomograms for recommended daily doses derived from the refined formula can be used in clinical practice to achieve the target AUC ensuring efficacy and safety of S‐1. [ABSTRACT FROM AUTHOR]

Background: Although colorectal mucinous adenocarcinomas (MCs) are conventionally regarded as exhibiting high-grade differentiation, they can be divided by differentiation into 2 groups according to the glandular appearance: low-grade mucinous adenocarcinoma (low-MC) and high-grade mucinous adenocarcinoma (high-MC). Methods: Patients with colorectal cancer (CRC) who underwent surgical resection between 2000 and 2012 were enrolled in this study. Among the cases with MC, the clinicopathological and genetic differences between low-MC and high-MC were investigated with next-generation sequencing. Results: A total of 1373 patients with CRC were analyzed. Forty patients (2.9%) had MC, and 13 patients had high-MC. Patients with MC had significantly shorter disease-free survival (DFS) and overall survival (OS) periods than those with nonmucinous carcinoma. When low-MC patients and high-MC patients were compared, those with high-MC had significantly shorter DFS and OS periods than those with low-MC. Multivariate analyses revealed that high-MC was significantly associated with both shorter DFS and shorter OS, but low-MC was not. A genome analysis revealed that low-MC had a considerably larger number of mutations than high-MC, and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and adenomatous polyposis coli mutations were particularly frequently found in low-MC. In contrast, SMAD family member 4 (SMAD4) mutations were frequently found in high-MC. Conclusions: High-MC is an independent prognostic factor in CRC (but low-MC is not), and it is genetically different from other CRCs, including low-MC. Both the clinicopathological differences and the genetic differences suggest that low-MC and high-MC should be distinguished in clinical settings. [ABSTRACT FROM AUTHOR]