Clin Cancer Res
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Obesity is associated with an increased risk of colon cancer. However, the influence of body mass index (BMI) on the prognosis of colon cancer survivors and its relationship to gender remains unknown. ⋯ Obesity is an independent prognostic variable in colon cancer survivors and shows gender-related differences. These data suggest that obesity-related biological factors can influence clinical outcome.
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Any drug product not previously authorized for marketing in the United States requires the submission of an Investigational New Drug application (IND). Although the IND submission is regulated by law (21CFR 312), there are several issues that are not covered in the law or U. S. ⋯ Most first-in-humans studies in oncology include patients with advanced and/or metastatic disease, as serious to severe side effects of anticancer therapies are often less threatening to advanced cancer patients than their disease, and acceptable levels of toxicity are higher. For other indications (adjuvant therapy, chemoprevention, or healthy volunteers), first-in-human studies need to follow ICH M3 guidelines as the risk to benefit ratio in those subjects and/or patients without evidence of tumor is different. The division welcomes submissions before the IND, also known as pre-INDs, particularly for products with "atypical issues."
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Randomized Controlled Trial
IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group.
Recent studies have shown the prognostic significance of IDH1 mutations in glioma. It is yet unclear if IDH1 mutations are predictive for outcome to chemotherapy. We determined the effect of IDH1 mutations on progression-free survival and overall survival (OS), and its correlation with other clinical and molecular features in the prospective randomized European Organization for Research and Treatment of Cancer study 26951 on adjuvant procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea, and vincristine (PCV) in anaplastic oligodendroglioma. ⋯ In this homogeneously treated group of anaplastic oligodendroglioma patients, the presence of IDH1 mutations was found to carry a very strong prognostic significance for OS but without evidence of a predictive significance for outcome to PCV chemotherapy. IDH1 mutations were strongly associated with 1p/19q codeletion and MGMT promoter methylation.
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HER2 amplification occurs in 18% to 27% of gastric and gastroesophageal junction cancers. Lapatinib, a potent ATP-competitive inhibitor simultaneously inhibits both EGFR and HER2. To explore the role of HER family biology in upper gastrointestinal cancers, we evaluated the effect of lapatinib, erlotinib, and trastuzumab in a panel of molecularly characterized human upper gastrointestinal cancer cell lines and xenografts. ⋯ Together, these data suggest that lapatinib has activity in HER2-amplified upper gastrointestinal cancer and supports the ongoing clinical investigation of lapatinib in patients with HER2-amplified disease.