Clin Cancer Res
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Randomized Controlled Trial Multicenter Study
Aspirin, NSAIDs, and risk of prostate cancer: results from the REDUCE study.
A recent meta-analysis showed that aspirin was associated with reduced prostate cancer risk. As anti-inflammatory medications lower PSA levels, whether these findings reflect reduced prostate cancer detection or lower prostate cancer risk is unknown. We tested the association between aspirin and nonaspirin NSAID use on prostate cancer diagnosis in REDUCE, where all men received biopsies at 2 and 4 years largely independent of PSA. REDUCE tested dutasteride for prostate cancer risk reduction in men with a PSA of 2.5 to 10.0 ng/mL and a negative prestudy biopsy. ⋯ Among men with a negative biopsy, aspirin and/or NSAID use was associated with decreased prostate cancer risk. Additional studies are warranted.
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Multicenter Study
Phase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655 (CH4987655) in selected patients with advanced cancer with RAS-RAF mutations.
This phase I expansion study assessed safety, pharmacodynamic effects, and antitumor activity of RO4987655, a pure MEK inhibitor, in selected patients with advanced solid tumor. ⋯ Safety profile of RO4987655 was comparable with other MEK inhibitors. Single-agent activity was observed in all entities except colorectal cancer. Evidence of target modulation and early biologic activity was shown among all indications independent of mutational status. Clin Cancer Res; 20(16); 4251-61. ©2014 AACR.
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Multicenter Study Clinical Trial
Population pharmacokinetics of bevacizumab in children with osteosarcoma: implications for dosing.
To describe sources of interindividual variability in bevacizumab disposition in pediatric patients and explore associations among bevacizumab pharmacokinetics and clinical wound healing outcomes. ⋯ A population pharmacokinetic model for bevacizumab was developed, which demonstrated that variability in bevacizumab exposure using weight-based dosing is related to body composition. Bevacizumab dosage scaling using ideal body weight would provide an improved dosing approach in children by minimizing pharmacokinetic variability and reducing likelihood of major wound healing complications.
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This phase I trial was undertaken to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the novel smoothened inhibitor sonidegib (LDE225), a potent inhibitor of hedgehog signaling, in patients with advanced solid tumors. ⋯ Sonidegib has an acceptable safety profile in patients with advanced solid tumors and exhibits antitumor activity in advanced BCC and relapsed medulloblastoma, both of which are strongly associated with activated hedgehog pathway, as determined by gene expression.
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Multicenter Study
Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer.
Patients with hormone receptor-negative breast cancer generally do not benefit from endocrine-targeted therapies. However, a subset with androgen receptor (AR) expression is predicted to respond to antiandrogen therapies. This phase II study explored bicalutamide in AR-positive, estrogen receptor (ER), and progesterone receptor (PgR)-negative metastatic breast cancer. ⋯ AR was expressed in 12% of patients with ER/PgR-negative breast cancer screened for this trial. The CBR of 19% observed with bicalutamide shows proof of principle for the efficacy of minimally toxic androgen blockade in a select group of patients with ER/PgR-negative, AR-positive breast cancer.