Diverse types of therapy-resistant prostate cancers are sensitive to a new combination of drugs that inhibit protein synthesis pathways in cancer cells.

IMPORTANCE-Obesity affects nearly one sixth of U.S. children and results in alterations to body composition and physiology that can affect drug disposition, possibly leading to therapeutic failure or toxicity. The depth of available literature regarding obesity's effect on drug safety, pharmacokinetics (PK) and dosing in obese children is unknown.OBJECTIVE-To perform a systematic literature review describing the current evidence of the effect of obesity on drug disposition in children. EVIDENCE REVIEW-We searched the Medline, Cochrane, and Embase databases (January 1970-December 2012 and included studies if they contained clearance, volume of distribution, or drug concentration data in obese children (age ≤18 years). We compared exposure and weightnormalized volume of distribution and clearance between obese and non-obese children.

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Background Brain metastases are common in advanced melanoma and often necessitate corticosteroids such as dexamethasone to control symptoms and reduce peritumoral edema. Immunotherapy improves survival in metastatic melanoma, but concomitant treatment with corticosteroids may reduce efficacy. Here, we report the use of bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, as a steroid‐sparing agent in melanoma patients with brain metastases treated with immunotherapy. Methods Medical records and imaging were retrospectively analyzed for melanoma patients with brain metastases who received bevacizumab at our institution between 2012 and 2017. Results 12 melanoma patients with brain metastases received bevacizumab (5‐7.5 mg/kg Q2‐3 W; median 4 cycles, range 1‐9). Patients were BRAF wild‐type or resistant to BRAF/MEK inhibitor therapy. All had progressive intracranial disease after prior resection, stereotactic radiosurgery and/or whole brain radiotherapy, and up to four lines of previous systemic treatment. Prior to bevacizumab, all patients had radiologically defined peritumoral edema and nine required dexamethasone for symptom control. In 10 evaluable patients, six reduced their dexamethasone dose by more than 50%, and eight displayed reduced edema 4 weeks after bevacizumab. Seven patients experienced adverse events possibly related to bevacizumab, including intracranial hemorrhage, hypertension, and gastrointestinal bleeding. Ten patients received immunotherapy after bevacizumab. Five patients survived more than 6 months, including one who remained disease‐free after 4 years and without neurological deficit despite being hemiplegic from edematous brain metastases prior to bevacizumab. Conclusion In 12 very poor prognosis melanoma patients with brain metastases, bevacizumab was well‐tolerated, associated with improved symptoms and reduced peritumoral edema despite weaning steroids, and facilitated treatment with immunotherapy that provided durable survival in a substantial proportion of cases.