Showing papers by "Eunice L. Kwak published in 2009"
TL;DR: EML4-ALK defines a molecular subset of NSCLC with distinct clinical characteristics and patients who harbor this mutation do not benefit from EGFR TKIs and should be directed to trials of ALK-targeted agents.
Abstract: Purpose The EML4-ALK fusion oncogene represents a novel molecular target in a small subset of non–small-cell lung cancers (NSCLC). To aid in identification and treatment of these patients, we examined the clinical characteristics and treatment outcomes of patients who had NSCLC with and without EML4-ALK. Patients and Methods Patients with NSCLC were selected for genetic screening on the basis of two or more of the following characteristics: female sex, Asian ethnicity, never/light smoking history, and adenocarcinoma histology. EML4-ALK was identified by using fluorescent in situ hybridization for ALK rearrangements and was confirmed by immunohistochemistry for ALK expression. EGFR and KRAS mutations were determined by DNA sequencing. Results Of 141 tumors screened, 19 (13%) were EML4-ALK mutant, 31 (22%) were EGFR mutant, and 91 (65%) were wild type (WT/WT) for both ALK and EGFR. Compared with the EGFR mutant and WT/WT cohorts, patients with EML4-ALK mutant tumors were significantly younger (P < .001 and ...
1,733 citations
TL;DR: Sunitinib shows evidence of modest antitumor activity in advanced HCC with manageable adverse effects and Rapid changes in tumor vascular permeability and circulating inflammatory biomarkers are potential determinants of response and resistance to sunitinIB in HCC.
Abstract: Purpose To assess the safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma (HCC) and explore biomarkers for sunitinib response. Patients and Methods We conducted a multidisciplinary phase II study of sunitinib, an antivascular endothelial growth factor receptor tyrosine kinase inhibitor, in advanced HCC. Patients received sunitinib 37.5 mg/d for 4 weeks followed by 2 weeks of rest per cycle. The primary end point was progression-free survival (PFS). We used functional magnetic resonance imaging to evaluate vascular changes in HCC after sunitinib treatment. Circulating molecular and cellular biomarkers were evaluated before and at six time points after sunitinib treatment. Results Thirty-four patients were enrolled. The objective response rate was 2.9%, and 50% of patients had stable disease. Median PFS was 3.9 months (95% CI, 2.6 to 6.9 months), and overall survival was 9.8 months (95% CI, 7.4 months to not available). Grade 3 or 4 toxicities included leukopenia/neutropenia,...
463 citations
TL;DR: These results underscore the potential of mutational profiling to identify CRCs with different natural histories or treatment responses and the adverse significance of BRAF mutation should inform patient selection and stratification in clinical trials.
Abstract: We address the prognostic and predictive value of KRAS, PIK3CA and BRAF mutations for clinical outcomes in response to active agents in the treatment of metastatic colorectal cancer (mCRC). We determined KRAS, BRAF and PIK3CA mutations in tumours from 168 patients treated for mCRC at two institutions. All patients received 5-FU-based first-line chemotherapy and treatment outcome was analysed retrospectively. KRAS, BRAF and PIK3CA mutations were present in 62 (37%), 13 (8%) and 26 (15%) cases, respectively. Multivariate analysis uncovered BRAF mutation as an independent prognostic factor for decreased survival (hazard ratio (HR) 4.0, 95% confidence interval (CI) 2.1–7.6). In addition, patients with BRAF-mutant tumours had significantly lower progression-free survival (PFS: HR 4.0, 95% CI 2.2–7.4) than those whose tumors that carried wild-type BRAF. Among 92 patients treated using chemotherapy and cetuximab as salvage therapy, KRAS mutation was associated with lack of response (P=0.002) and shorter PFS (P=0.09). BRAF (P=0.0005) and PIK3CA (P=0.01) mutations also predicted reduced PFS in response to cetuximab salvage therapy. These results underscore the potential of mutational profiling to identify CRCs with different natural histories or treatment responses. The adverse significance of BRAF mutation should inform patient selection and stratification in clinical trials.
288 citations
TL;DR: PF-02341066 (PF) is a small molecule oral inhibitor of the c-Met/HGFR and ALK receptor tyrosine kinases that has not previously been tested in humans as discussed by the authors.
Abstract: 3509 Background: PF-02341066 (PF) is a selective, ATP-competitive, small molecule oral inhibitor of the c-Met/HGFR and ALK receptor tyrosine kinases that has not previously been tested in humans. A...
191 citations
TL;DR: Exposure to XL147 reduced levels of phosphorylated PI3K pathway components in PBMCs, hair, skin, and tumor tissues in an exposure-dependent manner and was generally well tolerated with the MTD for the 21/7 schedule defined as 600 mg.
Abstract: 3500 Background: XL147 is a selective inhibitor of Class I PI3K isoforms. In preclinical cancer models XL147 is cytostatic or cytoreductive as monotherapy and enhances the efficacy of targeted agen...
59 citations
TL;DR: Bva and erl in combination with infusional 5-FU and RT appears to be a highly active preoperative regimen for locally advanced rectal cancer.
Abstract: 4106 Background: The German Rectal Cancer Study Group established neoadjuvant therapy as a standard of care in patients with T3/T4 rectal cancer. Beva, a vascular endothelial growth factor (VEGF) i...
11 citations
TL;DR: In this article, Vascular endothelial growth factor (VEGF) expression is present in BTCs and is associated with poor survival, and the authors performed a phase II study to examine the efficacy and tolerability of the VGF-based drug.
Abstract: 4578 Background: Vascular endothelial growth factor (VEGF) expression is present in BTCs and is associated with poor survival. We performed a phase II study to examine the efficacy and tolerability...
4 citations
TL;DR: From the Divisions of Hematology– Oncology (E.L.K.) and Gastroenterology (D.G.F.), Department of Medicine, and the Departments of Radiation Oncologists (T.S.F), Radiology (R.N.B.), Radiology(R.Y.U.), and Pathology (G.L.), Harvard Medical School.
Abstract: A 63-year-old woman was seen for management of adenocarcinoma of the gastroesophageal junction. Two months earlier, dysphagia had developed. Endoscopic, radiologic, and pathological evaluation disclosed adenocarcinoma at the gastroesophageal junction, associated with Barrett's esophagus, and possible metastatic cancer in a regional lymph node. A treatment plan was established.
3 citations