Sorafenib and everolimus in patients with advanced solid tumors and KRAS-mutated NSCLC: A phase I trial with early pharmacodynamic FDG-PET assessment.

BACKGROUND: Treatment of patients with solid tumors and KRAS mutations remains disappointing. One option is the combined inhibition of pathways involved in RAF-MEK-ERK and PI3K-AKT-mTOR. METHODS: Patients with relapsed solid tumors were treated with escalating doses of everolimus (E) 2.5-10.0 mg/d in a 14-day run-in phase followed by combination therapy with sorafenib (S) 800 mg/d from day 15. KRAS mutational status was assessed retrospectively in the escalation phase. Extension phase included KRAS-mutated non-small-cell lung cancer (NSCLC) only. Pharmacokinetic analyses were accompanied by pharmacodynamics assessment of E by FDG-PET. Efficacy was assessed by CT scans every 6 weeks of combination. RESULTS: Of 31 evaluable patients, 15 had KRAS mutation, 4 patients were negative for KRAS mutation, and the KRAS status remained unknown in 12 patients. Dose-limiting toxicity (DLT) was not reached. The maximum tolerated dose (MTD) was defined as 7.5 mg/d E + 800 mg/d S due to toxicities at previous dose level (10 mg/d E + 800 mg/d S) including leucopenia/thrombopenia III° and pneumonia III° occurring after the DLT interval. The metabolic response rate in FDG-PET was 17% on day 5 and 20% on day 14. No patient reached partial response in CT scan. Median progression free survival (PFS) and overall survival (OS) were 3.25 and 5.85 months, respectively. CONCLUSIONS: Treatment of patients with relapsed solid tumors with 7.5 mg/d E and 800 mg/d S is safe and feasible. Early metabolic response in FDG-PET was not confirmed in CT scan several weeks later. The combination of S and E is obviously not sufficient to induce durable responses in patients with KRAS-mutant solid tumors.

Early Recognition of the Preference for Exclusive Breastfeeding in Current China: A Prediction Model based on Decision Trees.

Exclusive breastfeeding (EBF) is affected by multiple risk factors. Therefore, it is difficult for clinical professionals to identify women who will not practice EBF well and provide subsequent medical suggestions and treatments. This study aimed to apply a decision tree (DT) model to predict EBF at two months postpartum. The socio-demographic, clinical and breastfeeding parameters of 1,141 breastfeeding women from Nanjing were evaluated. Decision tree modelling was used to analyse and screen EBF factors and establish a risk assessment model of EBF. The Chinese version of the Breastfeeding Self-Efficacy Scale (CV-BSES) score, early formula supplementation, abnormal nipples, mastitis, neonatal jaundice, cracked or sore nipples and intended duration of breastfeeding were significant risk factors associated with EBF in the DT model. The accuracy, sensitivity and specificity of the DT model were 73.1%, 75.5% and 66.3%, respectively. The DT model showed similar or better performance than the logistic regression model in assessing the risk of early cessation of EBF before two months postpartum. The DT model has potential for application in clinical practice and identifies high-risk subpopulations that need specific prevention.