Multicenter Phase II Trial of Axitinib Monotherapy for Gemcitabine-Based Chemotherapy Refractory Advanced Biliary Tract Cancer (AX-BC Study).

LESSONS LEARNED: Axitinib exhibited marginal activity against gemcitabine-refractory unselected biliary tract cancer. Pretreated soluble vascular endothelial growth factor receptor-2 may be a useful biomarker for axitinib treatment outcome. Ascites should be carefully monitored in patients receiving anti-vascular endothelial growth factor receptor therapy including axitinib in advanced biliary tract cancer. BACKGROUND: There are no clear options for second-line treatment in patients with gemcitabine (GEM)-refractory biliary tract cancer (BTC). We conducted a multicenter, single-arm, phase II trial to confirm the efficacy and safety of axitinib, a potent selective inhibitor of vascular endothelial growth factor receptor (VEGFR)-1/2/3, in patients with GEM-refractory BTC. METHODS: Patients refractory or intolerant to GEM-based chemotherapy were enrolled. Axitinib was administered orally at an initial dose of 5 mg twice daily. The primary endpoint was progression-free survival (PFS), and the threshold and expected values were set at 2 and 3 months, respectively. The target sample size was 32 patients. RESULTS: Nineteen patients were enrolled. The trial was interrupted for a total of 13 months for the evaluation of adverse events. Thirteen patients were previously treated with ≥2 regimens. The median PFS was 2.8 months (95% confidence interval [CI]: 2.1-4.1). The median overall survival was 5.8 months (95% CI: 3.3-9.7). The response rate was 5.3% (95% CI: 0.0-15.3). Grade 3 ascites occurred in two patients. Baseline soluble VEGFR-2 levels were significantly associated with PFS. CONCLUSION: Axitinib exhibited marginal activity against GEM-refractory BTC. Ascites should be carefully monitored in axitinib-treated patients with advanced BTC.

[The Risk Factors of Cancer Chemotherapy in Elderly Patients].

The aging rate in Japan is the highest in the world, and it is entering a very aging society that has never happened before. The first cause of death is a malignant neoplasm, and opportunities of the treatment for elderly cancer patients are rapidly increasing. The elderly have increased chronic diseases and complications with aging, and the adverse event in medication therapy also increases. Also, the form of medical provision is diversified, home medical care and nursing care are recommended. Therefore, it is important to appreciate the various aspects including psychophysiological, living, social aspects in addition to changes in physical function caused by aging and appropriately evaluate them, for selecting treatment methods in elderly cancer patients. Geriatric assessment(GA)is recommended for this evaluation, and it is expected to contribute to improvement of treatment outcome and quality of life(QOL). In this article, we will outline the role of aged general comprehensive functional evaluation in elderly cancer treatment and the problems of chemotherapy in the elderly.

[Geriatric Oncology].

The number of older adults in Japan is rising, and healthcare for older patients differs from those of younger patients.We have limited available data regarding the outcomes of cancer treatment in this population.In addition, we have few guidelines to address the evaluation and treatment of older cancer patients in Japan.The Japan Agency for Medical Research and Development(AMED)has funded clinical research focusing on elderly cancer patients.We organized the Geriatric Study Committee in Japan Clinical Oncology Group(JCOG)to develop geriatric research policy in this area.This policy includes the (1)definition of a selection policy for the subjects of geriatric research,(2)establishment of standard endpoints and methodological schemes for geriatric research, and(3)recommendations for standard tools of geriatric assessment.We are also developing a curriculum in geriatric oncology for medical doctors and oncology nurses to improve the evidence-based evaluation and treatment of elderly cancer patients.Japanese society is progressing to address the increasing number of elderly patients using a team approach in a broad sense, which consists of cancer professionals, healthcare providers, and government.

The effect of real-time monitoring of physical activity intensity in diabetic patients.

AIM: To evaluate the effects of an intensity display type accelerometer on diabetic patients' physical activity. METHODS: This was a two-arm, non-randomized controlled study. Both groups received information about the recommendation of 150 min/week moderate-to-vigorous physical activity (MVPA). The intervention group used an intensity display type accelerometer to monitor their physical activity intensity for 10 days at baseline and 3 months later. We compared intervention and control groups after 3 and 6 months. Primary outcomes were MVPA and number of steps over 7 days. Secondary outcomes were glycosylated hemoglobin (HbA1c), body mass index, and self-management. RESULTS: Of 62 participants, 30 and 32 were included in the intervention and control groups, respectively. Mean age in each group was 59.7 ± 10.8 and 58.8 ± 10.2 years, and mean HbA1c was 6.9 ± 0.9% and 6.9 ± 0.8%, respectively. There were no significant differences between the intervention and control groups at either time point, and no outcomes showed significant changes. In a subgroup analysis by physical activity intensity, MVPA of active individuals in the control group significantly decreased at 6 months from baseline. MVPA and number of steps among inactive individuals in the intervention group significantly increased at 6 months from baseline. Self-management of the intervention group showed a trend toward improvement, but HbA1c and body mass index showed no significant change. CONCLUSIONS: Monitoring physical activity intensity led to increased MVPA of inactive patients and maintained MVPA of active patients with diabetes mellitus. This straightforward intervention could be applied in clinical practice.

Moderate-to-vigorous physical activity and the risk of stroke recurrence in patients with a history of minor ischemic stroke in Japan: a retrospective analysis.

BACKGROUND: Physical activity (PA) is beneficial for stroke prevention; in particular, moderate-to-vigorous physical activity (MVPA). However, few studies have investigated its relationship with recurrent ischemic stroke (RIS). OBJECTIVES: To clarify the relationship between MVPA and RIS and the burden of risk factors after a first-ever ischemic stroke. METHODS: A total of 45 outpatients (mean age 67.1 ± 10.2 years) who had previously experienced a transient ischemic attack or a minor non-cardioembolic ischemic stroke at a single hospital in Japan (mean 6.4 ± 4.2 years previously), were enrolled between March and June 2016. All patients wore an accelerometer around their hips for 10 days, and their percentage body fat (%BF) and visceral fat level (VFL) were measured by bioelectrical impedance. Retrospective information about the history of RIS and risk factors (blood pressure, lipoprotein cholesterol and estimated glomerular filtration rate) were extracted from the clinical records. Binary logistic regression models were used to estimate the relevance of the RIS history to MVPA and potential risk factors such as sociodemographic and clinical variables (obesity, smoking and hypertension). RESULTS: RIS occurred in 9 patients; they had significantly higher VFL (p = 0.007) and %BF (p = 0.007) values and lower MVPA (p = 0.011) values than patients without recurrence. A multivariate analysis of these factors indicated that age, VFL and MVPA were significant independent predictors of RIS. CONCLUSIONS: Patients with a history of mild ischemic stroke had low MVPA and high VFL values, which together may be a risk factor for RIS.