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BackgroundAnlotinib is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR α/β, c-Kit, and Ret. We aimed to evaluate the safety, pharmacokinetics, and antitumor activity of anlotinib in patients with advanced refractory solid tumors.MethodsAnlotinib (5–16 mg) was orally administered in patients with solid tumor once a day on two schedules: (1) four consecutive weeks (4/0) or (2) 2-week on/1-week off (2/1). Pharmacokinetic sampling was performed in all patients. Twenty-one patients were further enrolled in an expanded cohort study on the recommended dose and schedule. Preliminary tumor response was also assessed.ResultsOn the 4/0 schedule, dose-limiting toxicity (DLT) was grade 3 hypertension at 10 mg. On the 2/1 schedule, DLT was grade 3 hypertension and grade 3 fatigue at 16 mg. Pharmacokinetic assessment indicated that anlotinib had long elimination half-lives and significant accumulation during multiple oral doses. The 2/1 schedule was selected, with 12 mg once daily as the maximum tolerated dose for the expanding study. Twenty of the 21 patients (with colon adenocarcinoma, non-small cell lung cancer, renal clear cell cancer, medullary thyroid carcinoma, and soft tissue sarcoma) were assessable for antitumor activity of anlotinib: 3 patients had partial response, 14 patients had stable disease including 12 tumor burden shrinkage, and 3 had disease progression. The main serious adverse effects were hypertension, triglyceride elevation, hand-foot skin reaction, and lipase elevation.ConclusionsAt the dose of 12 mg once daily at the 2/1 schedule, anlotinib displayed manageable toxicity, long circulation, and broad-spectrum antitumor potential, justifying the conduct of further studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0332-8) contains supplementary material, which is available to authorized users.

Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. Compared to the effect of placebo, it improved both progression-free survival (PFS) and overall survival (OS) in a phase III trial in patients with advanced non-small-cell lung cancer (NSCLC), despite progression of the cancer after two lines of prior treatments. Recently, the China Food and Drug Administration (CFDA) approved single agent anlotinib as a third-line treatment for patients with advanced NSCLC. Moreover, a randomized phase IIB trial demonstrated that anlotinib significantly prolonged the median PFS in patients with advanced soft tissue sarcoma (STS). Anlotinib also showed promising efficacy in patients with advanced medullary thyroid carcinoma and metastatic renal cell carcinoma (mRCC). The tolerability profile of anlotinib is similar to that of other tyrosine kinase inhibitors that target VEGFR and other tyrosine kinase-mediated pathways; however, anlotinib has a significantly lower incidence of grade 3 or higher side effects compared to that of sunitinib. We review the rationale, clinical evidence, and future perspectives of anlotinib for the treatment of multiple cancers.

The prognosis for patients with refractory soft-tissue sarcoma (STS) is dismal. Anlotinib has previously shown antitumor activity on STS in preclinical and phase I studies. Patients 18 years and older, progressing after anthracycline-based chemotherapy, naïve from angiogenesis inhibitors, with at least one measurable lesion according to RECIST 1.1, were enrolled. The main subtypes eligible were undifferentiated pleomorphic sarcoma (UPS), liposarcoma (LPS), leiomyosarcoma (LMS), synovial sarcoma (SS), fibrosarcoma (FS), alveolar soft-part sarcoma (ASPS), and clear cell sarcoma (CCS). Participants were treated with anlotinib. The primary endpoint was progression-free rate at 12 weeks (PFR). A total of 166 patients were included in the final analysis. Overall, the PFR was 68%, and objective response rate was 13% (95% confidence interval, 7.6%-18%). The median progression-free survival (PFS) and overall survival (OS) were 5.6 and 12 months, respectively. The PFR, median PFS and OS were: 58%, 4.1 and 11 months for UPS ( = 19); 63%, 5.6 and 13 months for LPS ( = 13); 75%, 11 and 15 months for LMS ( = 26); 75%, 7.7 and 12 months for SS ( = 47); 81%, 5.6 and 12 months for FS ( = 18); 77%, 21 and not reached for ASPS ( = 13); 54%, 11 and 16 months for CCS ( = 7); and 44%, 2.8 and 8.8 months for other sarcoma ( = 23), respectively. The most common clinically significant grade 3 or higher adverse events were hypertension (4.8%), triglyceride elevation (3.6%), and pneumothorax (2.4%). No treatment-related death occurred. Anlotinib showed antitumor activity in several STS entities. The toxicity was manageable. .

The six weeks of group tai chi followed by another six weeks of home tai chi training showed significant improvements in mean overall knee pain (P = 0.0078), maximum knee pain (P = 0.0035) and the WOMAC subscales of physical function (P = 0.0075) and stiffness (P = 0.0206) compared to the baseline. No significant change of any outcome measure was noted in the attention control group throughout the study. The tai chi group reported lower overall pain and better WOMAC physical function than the attention control group at weeks 9 and 12. All improvements disappeared after detraining.

The 44-item and 10-item Big Five Inventory (BFI) personality scales are widely used, but there is a lack of psychometric data for Chinese versions. Eight surveys (total N = 2,496, aged 18–82), assessed a Chinese-language BFI-44 and/or an independently translated Chinese-language BFI-10. Most BFI-44 items loaded strongly or predominantly on the expected dimension, and values of Cronbach's alpha ranged .698-.807. Test-retest coefficients ranged .694-.770 (BFI-44), and .515-.873 (BFI-10). The BFI-44 and BFI-10 showed good convergent and discriminant correlations, and expected associations with gender (females higher for agreeableness and neuroticism), and age (older age associated with more conscientiousness and agreeableness, and also less neuroticism and openness). Additionally, predicted correlations were found with chronotype (morningness positive with conscientiousness), mindfulness (negative with neuroticism, positive with conscientiousness), and mind wandering/daydreaming frequency (negative with conscientiousness, positive with neuroticism). Exploratory analysis found that the Self-discipline facet of conscientiousness positively correlated with morningness and mindfulness, and negatively correlated with mind wandering/daydreaming frequency. Furthermore, Self-discipline was found to be a mediator in the relationships between chronotype and mindfulness, and chronotype and mind wandering/daydreaming frequency. Overall, the results support the utility of the BFI-44 and BFI-10 for Chinese-language big five personality research.

The study of the origin of spouse similarity is interesting because the extent to which spouse similarity reflects genetic resemblance between husbands and wives affects the genetic structure of a population. The sources of observed spouse similarity in attitudes, personality, and psychological well-being are discussed. Analyses based on data collected from an American adult sample assessed longitudinally showed that spouse correlations were high for attitudes and low to moderate for personality and psychological well-being. Four competing explanations to spouse similarity were compared: initial similarity, attrition, convergence, and age covariation. The results did not support the latter three explanations, indicating that initial similarity may be an appropriate interpretation of observed spouse similarity. The findings are consistent with those of other comparable studies.

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