Search results for " RAS"
showing 10 items of 218 documents
Management of Toxicity Induced by Anti-EGFR Therapy in Metastatic Colorectal Cancer
2013
Use of anti-epidermal growth factor receptor (anti-EGFR) agents has yielded significant advances in the treatment of patients with metastatic colorectal cancer. In fact these drugs, which include the monoclonal antibodies cetuximab and panitumumab, can be delivered both as a single agent and in combination with chemotherapy, achieving better survival and quality of life and in some cases also resectability of metastases. However, these agents can result in the development of toxicities that are usually different from those observed with chemotherapy alone. For the management of these adverse effects, proper knowledge is mandatory. Skin toxicity is the most frequent adverse effect. Other tox…
Cetuximab plus FOLFOX-4 in untreated patients with advanced colorectal cancer: a Gruppo Oncologico dell'Italia Meridionale Multicenter phase II study.
2010
<i>Objectives:</i> FOLFOX-4 and FOLFIRI are considered equivalent in terms of activity and efficacy as first-line chemotherapy in metastatic colorectal cancer (mCRC). The monoclonal antibody (mAb) cetuximab showed intrinsic activity as a single agent in mCRC and was approved in combination with CPT-11 for patients who failed previous CPT-11-based treatment. The purpose of this phase II study was to evaluate the activity and safety of FOLFOX-4 plus cetuximab in untreated mCRC patients. <i>Methods:</i> Untreated patients with measurable metastatic disease and expressing epidermal growth factor receptor (EGFR) received cetuximab at a loading dose of 400 mg/m<sup>2…
Patterns of K-ras mutation in colorectal carcinomas from Iran and Italy (a Gruppo Oncologico dell'Italia Meridionale study): influence of microsatell…
2006
Background: K-ras mutations are a key step in colorectal cancer progression. Such mutations have been widely studied in case series from Western countries but there are few data on the rate and spectrum of mutations in tumors from countries where the epidemiological features of the disease are different. Patients and methods: Tumor samples from 182 Iranian colorectal cancer patients (170 sporadic cases and 12 HNPCC cases) were screened for K-ras mutations at codons 12, 13 and 61 by sequencing analysis. The cases were also characterized for microsatellite instability at mononucleotide repeats by PCR and fragment analysis, and classified according to microsatellite instability status. The fre…
Biomarkers and efficacy: Are we nearly there yet?
2011
EDITORIAL
Analysis of KRAS/NRAS mutations in a phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic …
2015
Abstract Purpose: We evaluated the influence of RAS mutation status on the treatment effect of panitumumab in a prospective–retrospective analysis of a randomized, multicenter phase III study of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) versus FOLFIRI alone as second-line therapy in patients with metastatic colorectal cancer (mCRC; ClinicalTrials.gov, NCT0039183). Experimental Design: Outcomes were from the study's primary analysis. RAS mutations beyond KRAS exon 2 (KRAS exons 3, 4; NRAS exons 2, 3, 4; BRAF exon 15) were detected by bidirectional Sanger sequencing in wild-type KRAS exon 2 tumor specimens. Progression-free survival (PFS) and overall survival (OS) we…
Acquired BRAF inhibitor resistance: A multicenter meta-analysis of the spectrum and frequencies, clinical behaviour, and phenotypic associations of r…
2015
BackgroundAcquired resistance to BRAF inhibitors (BRAFi) is a near-universal phenomenon caused by numerous genetic and non-genetic alterations. In this study, we evaluated the spectrum, onset, pattern of progression, and subsequent clinical outcomes associated with specific mechanisms of resistance.MethodsWe compiled clinical and genetic data from 100 patients with 132 tissue samples obtained at progression on BRAFi therapy from 3 large, previously published studies of BRAFi resistance. These samples were subjected to whole-exome sequencing and/or polymerase chain reaction-based genetic testing.ResultsAmong 132 samples, putative resistance mechanisms were identified in 58%, including NRAS o…
Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial.
2011
Abstract Hydroxyurea is the standard therapy of chronic myelomonocytic leukemia (CMML) presenting with advanced myeloproliferative and/or myelodysplastic features. Response to hypomethylating agents has been reported in heterogeneous series of CMML. We conducted a phase 2 trial of decitabine (DAC) in 39 patients with advanced CMML defined according to a previous trial. Median number of DAC cycles was 10 (range, 1-24). Overall response rate was 38% with 4 complete responses (10%), 8 marrow responses (21%), and 3 stable diseases with hematologic improvement (8%). Eighteen patients (46%) demonstrated stable disease without hematologic improvement, and 6 (15%) progressed to acute leukemia. With…
Heterogeneity of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer and potential effects on therapy in the CAPRI GOIM trial
2015
Background: Evidence suggests that metastatic colorectal carcinoma (mCRC) has a high level of intratumor heterogeneity. We carried out a quantitative assessment of tumor heterogeneity for KRAS, NRAS, BRAF and PIK3CA mutations, in order to assess potential clinical implications. Patients and methods: Tumor samples (n = 182) from the CAPRI-GOIM trial of first-line cetuximab + FOLFIRI in KRAS exon-2 wild-type mCRC patients were assessed by next-generation sequencing that allows quantitative assessment of mutant genes. Mutant allelic frequency was normalized for the neoplastic cell content and, assuming that somatic mutations usually affect one allele, the Heterogeneity Score (HS) was calculate…
Impact of Baseline Covariates and Prior Therapy on the Efficacy of Second-Line Panitumumab (Pmab) + Folfiri Vs Folfiri Treatment
2014
ABSTRACT Aim: Expanding RAS analyses beyond KRAS exon 2 is important in selecting patients (pts) for pmab treatment. Here we present prespecified subgroup analyses from a phase 3 randomised second-line pmab + FOLFIRI vs FOLFIRI study in metastatic colorectal cancer (mCRC) pts. Methods: Progression-free (PFS) and overall survival (OS) were co-primary endpoints. KRAS exon 2 wild-type (WT) samples were tested for mutations in KRAS exons 3/4, NRAS exons 2/3/4 and BRAF exon 15 via bidirectional Sanger sequencing and WAVE-based SURVEYOR®. PFS and OS subgroup analyses were performed by randomisation stratification factors (ECOG performance status [PS], prior bevacizumab [bev]/prior oxaliplatin [ox…
New findings on primary and acquired resistance to anti-EGFR therapy in metastatic colorectal cancer: Do all roads lead to RAS?
2015
Abstract: Anti-epidermal growth factor receptor therapy with the monoclonal antibodies cetuximab and panitumumab is the main targeted treatment to combine with standard chemotherapy for metastatic colorectal cancer. Many clinical studies have shown the benefit of the addition of these agents for patients without mutations in the EGFR pathway. Many biomarkers, including KRAS and NRAS mutations, BRAF mutations, PIK3CA mutations, PTEN loss, AREG and EREG expression, and HER-2 amplification have already been identified to select responders to anti-EGFR agents. Among these alterations KRAS and NRAS mutations are currently recognized as the best predictive factors for primary resistance. Liquid b…