Developmental assessments during the first 5 years of life in infants fed breast milk, cow's milk formula, or soy formula.

OBJECTIVE: To investigate the effects of infant feeding mode on childhood cognition and language as the differential effects of infant feeding on development remain understudied. METHODS: Breastfed [BF, 174], cow's milk-based formula-fed [MF, 169], or soy protein-based formula-fed [SF, 161] children were longitudinally tested from age 3 to 60 months for neurodevelopment. Data were analyzed using mixed models while adjusting for multiple covariates. Sex differences were also assessed. RESULTS: Standard scores were within established norms for all groups. There were no differences in mental development to age 24 months, yet BF children had significantly higher motor development scores at age 3 months than SF children (99.1 versus. 97.2). BF children had significantly higher composite intelligence scores at 48 months than MF and SF children (113.4 versus. 109.6 and 108.4, respectively) and higher verbal intelligence scores than SF children at 48 (105.6 versus. 100.7) and 60 months (109.8 versus. 105.9). Greater total language scores at ages 36 and 48 months were found in BF children compared with children fed MF or SF (p < .001), with differences between sexes for auditory comprehension. Higher total language scores at age 60 months were found between BF and SF (105.0 versus. 100.1). CONCLUSION: Breastfeeding was associated with small, statistically significant, differences between children ages 3 and 5 years in verbal intelligence, expressive communication, and auditory comprehension with the latter having potential sexual dimorphic effects. Yet, these differences remain small and may not be of clinical relevance. Overall, MF and SF did not significantly differ.

Phase II results of Dovitinib (TKI258) in patients with metastatic renal cell cancer.

PURPOSE: Fibroblast growth factor (FGF) signaling regulates tumor growth and vascularization and partly mediates antiangiogenic escape from VEGF receptor (VEGFR) inhibitors. Dovitinib (TKI258) is a tyrosine kinase inhibitor (TKI) that inhibits FGF receptor (FGFR), VEGFR, and platelet-derived growth factor receptor, which are known drivers of antiangiogenic escape, angiogenesis, and tumor growth in renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: Patients with advanced or metastatic RCC were treated with oral dovitinib 500 mg/day (5-days-on/2-days-off schedule). The study population was enriched for patients previously treated with a VEGFR TKI and an mTOR inhibitor. RESULTS: Of 67 patients enrolled, 55 patients (82.1%) were previously treated with ≥1 VEGFR TKI and ≥1 mTOR inhibitor (per-protocol efficacy set). The 8-week overall response rate and disease control rate in this population were 1.8% and 52.7%, respectively. Disease control rate during the entire study period was 56.4% (50.9% ≥4 months). Median progression-free survival and overall survival in the entire population were 3.7 and 11.8 months, respectively. Pharmacodynamic analyses demonstrated dovitinib-induced inhibition of VEGFR (as determined by increased levels of placental growth factor and decreased levels of soluble VEGFR2) and FGFR (as determined by increased FGF23 serum measures). The most frequently reported treatment-related adverse events of all grades included nausea (65.7%), diarrhea (62.7%), vomiting (61.2%), decreased appetite (47.8%), and fatigue (32.8%). CONCLUSION: Dovitinib was shown to be an effective and tolerable therapy for patients with metastatic RCC who had progressed following treatment with VEGFR TKIs and mTOR inhibitors. Clin Cancer Res; 20(11); 3012-22. ©2014 AACR.

Temozolomide versus procarbazine, lomustine, and vincristine in recurrent high-grade glioma.

PURPOSE: Temozolomide (TMZ) is an alkylating agent licensed for treatment of high-grade glioma (HGG). No prospective comparison with nitrosourea-based chemotherapy exists. We report, to our knowledge, the first randomized trial of procarbazine, lomustine, and vincristine (PCV) versus TMZ in chemotherapy-naive patients with recurrent HGG. PATIENTS AND METHODS: Four hundred forty-seven patients were randomly assigned to PCV (224 patients) or TMZ (sub-random assignment: TMZ-5 [200 mg/m(2) for 5 days, 112 patients] or TMZ-21 [100 mg/m(2) for 21 days, 111 patients]) for up to 9 months or until progression. The primary outcomes were survival (PCV v TMZ) and 12-week progression-free survival (PFS; TMZ-5 v TMZ-21). This study is registered as ISRCTN83176944. RESULTS: Percentages of patients completing 9 months of treatment in the PCV, TMZ-5, and TMZ-21 arms were 17%, 26%, and 13%, respectively. Major toxicity was similar across all three groups. With a median follow-up time of 12 months and 382 deaths, there was no clear survival benefit when comparing PCV with TMZ (hazard ratio [HR], 0.91; 95% CI, 0.74 to 1.11; P = .350). For TMZ-5 versus TMZ-21, 12-week PFS rates were similar (63.6% and 65.7%, respectively; P = .745), but TMZ-5 improved overall PFS (HR, 1.38; 95% CI, 1.05 to 1.82; P = .023), survival (HR, 1.32; 95% CI, 0.99 to 1.75; P = .056), and global quality of life (49% v 19% improved > 10 points at 6 months, respectively; P = .005). CONCLUSION: Although TMZ (both arms combined) did not show a clear benefit compared with PCV, comparison of the TMZ schedules demonstrated that the 21-day schedule was inferior to the 5-day schedule in this setting. This challenges the current understanding of increasing TMZ dose-intensity by prolonged scheduling.