Journal of the National Cancer Institute
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J. Natl. Cancer Inst. · Dec 2012
Evaluation of excess statistical significance in meta-analyses of 98 biomarker associations with cancer risk.
Numerous biomarkers have been associated with cancer risk. We assessed whether there is evidence for excess statistical significance in results of cancer biomarker studies, suggesting biases. ⋯ Most well-documented biomarkers of cancer risk without evidence of bias pertain to infectious agents. Conversely, an excess of statistically significant findings was observed in studies of IGF/insulin and inflammation systems, suggesting reporting biases.
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J. Natl. Cancer Inst. · Dec 2012
Meta AnalysisMeta-analysis of the relationship between dose and benefit in phase I targeted agent trials.
To date, the primary objective of phase I trials has been to safely select the maximum tolerated dose (MTD) of a drug or drug combination for utilization in subsequent trials. Although conventional cytotoxic chemotherapy is generally more effective at the MTD than molecularly targeted agents (MTAs), recent single-institution data suggest that molecularly targeted agent may not require an MTD for efficacy. We analyzed patient outcome results in MTA phase I trials at multiple institutions throughout North America sponsored by the National Cancer Institute's Cancer Therapy Evaluation Program. ⋯ Patients treated in the context of phase I trials with MTAs continue to derive reasonable clinical benefit. Contrary to other single institution data, our data suggest clinical benefit in terms of increasing response and overall survival with increasing dose.