A phase I trial of the MEK inhibitor selumetinib (AZD6244) in pediatric patients with recurrent or refractory low-grade glioma: a Pediatric Brain Tumor Consortium (PBTC) study.

Background: Activation of the mitogen-activated protein kinase pathway is important for growth of pediatric low-grade gliomas (LGGs). The aim of this study was to determine the recommended phase II dose (RP2D) and the dose-limiting toxicities (DLTs) of the MEK inhibitor selumetinib in children with progressive LGG.

Methods: Selumetinib was administered orally starting at 33 mg/m2/dose b.

The Prevalence and Impact of Hyperglycemia and Hyperlipidemia in Patients With Advanced Cancer Receiving Combination Treatment With the Mammalian Target of Rapamycin Inhibitor Temsirolimus and Insulin Growth Factor-Receptor Antibody Cixutumumab.

Background: Cixutumumab (a humanized monoclonal antibody against insulin-like growth factor-1 receptor [IGF-1R]) and the mammalian target of rapamycin (mTOR) inhibitor temsirolimus were combined in a phase I study of patients with advanced cancer. We investigated the prevalence of metabolic toxicities, their management, and impact on outcome.

Methods: The temsirolimus dose was 25 mg or 37.

Incidence of mucositis in patients treated with temsirolimus-based regimens and correlation to treatment response.

Mucositis may limit the therapeutic window for mammalian target of rapamycin inhibitor-based combination therapy, necessitating treatment interruptions and/or dose reductions. Optimizing treatment or prophylactic interventions for mucositis will enable patients to continue effective treatment while maintaining good quality of life.

Phase I trial of cixutumumab combined with temsirolimus in patients with advanced cancer.

Purpose: Mammalian target of rapamycin (mTOR) inhibitors mediate AKT activation through a type 1 insulin-like growth factor receptor (IGF-1R)-dependent mechanism. Combining the mTOR inhibitor temsirolimus with cixutumumab, a fully human immunoglobulin G1 monoclonal antibody directed against IGF-1R, was expected to enhance mTOR-targeted anticancer activity by modulating resistance to mTOR inhibition. The objectives of this phase I study were to evaluate the tolerability and activity of temsirolimus and cixutumumab.