Background: In patients with advanced colorectal cancer, KRAS mutation status predicts response to treatment with monoclonal antibody targeting the epithelial growth factor receptor (EGFR). Recent reports have provided evidence that KRAS mutation status has prognostic value in patients with resectable colorectal liver metastases (CLM) irrespective of treatment with chemotherapy or anti-EGFR therapy. A meta-analysis was undertaken to clarify the impact of KRAS mutation on outcomes in patients with resectable CLM.Methods: PubMed, Embase and Cochrane Library databases were searched systematically to identify full-text articles reporting KRAS-stratified overall (OS) or recurrence-free (RFS) survival after resection of CLM. Hazard ratios (HRs) and 95 per cent c.i. from multivariable analyses were pooled in meta-analyses, and a random-effects model was used to calculate weight and overall results.
Results:The search returned 355 articles, of which 14, including 1809 patients, met the inclusion criteria. Eight studies reported OS after resection of CLM in 1181 patients. The mutation rate was 27⋅6 per cent, and KRAS mutation was negatively associated with OS (HR 2⋅24, 95 per cent c.i. 1⋅76 to 2⋅85). Seven studies reported RFS after resection of CLM in 906 patients. The mutation rate was 28⋅0 per cent, and KRAS mutation was negatively associated with RFS (HR 1⋅89, 1⋅54 to 2⋅32).Conclusion: KRAS mutation status is a prognostic factor in patients undergoing resection of colorectal liver metastases and should be considered in the evaluation of patients having liver resection.
14151 Background: Pancreatic cancer is virtually always lethal, and the only FDA-approved therapies- gemcitabine and erlotinib- produce objective responses in less than 10% of patients. Curcumin (diferuloyl methane) is a plant- derived compound that inhibits the nuclear factor-kappa B (NF-kappa B) transcription factor (central to pancreatic cancer growth) and has substantial antitumor activity in preclinical models. We evaluated the toxicity and anti-tumor activity of curcumin, and its impact on survival and biologic correlates. Methods: Patients received 8 grams of curcumin (Sabinsa Corp.) by mouth daily for two months. Maintenance therapy was continued at the same dose and schedule until disease progression. Results: Seventeen patients were enrolled as of the date of analysis. Six were inevaluable: noncompliance (n = 1), never dosed (n = 1), noted to have gastric obstruction after one dose (n = 1), and too early (n = 3). Eleven patients were evaluable for response and 15 were evaluable for toxicity. To date, four patients have stable disease (2+, 2+, 3+ and 7 months) and one patient had a brief partial remission (73% reduction in tumor size by RECIST) that lasted one month. No toxicities have been observed. Serum was available for evaluation of pre-and post-dose cytokine levels in thirteen patients. Interestingly, the patient with the partial remission had marked increases (4–35 fold) in serum IL-1 receptor antagonist, IL-6, IL-10 and IL-8 levels. One to three other patients also had post-treatment increases in one or more of the above cytokines, albeit to a lesser extent (2–6 fold). Conclusions: We conclude that curcumin is well tolerated and our preliminary results suggest biologic activity in pancreatic cancer. Supported in part by the National Cancer Institute grant R21 CA 104337–01, The Topfer Fund for Pancreatic Cancer and Pancreatic SPORE grant 1 P20 CA10193–03. No significant financial relationships to disclose.
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