Article

Optimal use of targeted agents for advanced gastrointestinal stromal tumours.

HELIOS Klinikum Bad Saarow, Bad Saarow, Germany.
Oncology (Impact Factor: 2.61). 04/2010; 78(2):130-40. DOI: 10.1159/000312655
Source: PubMed

ABSTRACT Imatinib is the recommended 1st-line treatment for a KIT-positive unresectable and/or metastatic gastrointestinal stromal tumour (GIST). However, some patients experience intolerance to imatinib and most patients will eventually experience disease progression while on imatinib treatment. Sunitinib is approved for treatment of a GIST after disease progression on, or intolerance to, imatinib therapy. Progression may occur early or later on, in treatment and is determined by factors including initial GIST genotype and mutational status. GISTs with KIT exon 11 mutations appear to be sensitive to standard dose imatinib, and patients with GISTs exhibiting KIT exon 9 mutations whose disease has progressed on imatinib 400 mg/day have been shown to respond to imatinib 800 mg/day, albeit with a higher incidence of adverse events. Sunitinib has shown clinical benefit in all major GIST mutational subtypes, particularly in patients with wild-type or KIT exon 9 genotype and against GISTs with secondary KIT exon 13 or 14 mutations. The choice between higher-dose imatinib and sunitinib after progression on standard dose imatinib is unclear, and apart from the GIST primary resistance genotype and mutational status, individual patient factors such as tumour characteristics, drug pharmacokinetics, and other clinical factors may affect response to treatment. Individualisation of therapy may help to maximise clinical benefit of therapy in these patients.

0 Followers
 · 
82 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Next-generation sequencing (NGS) approaches for measuring RNA and DNA benefit from greatly increased sensitivity, dynamic range and detection of novel transcripts. These technologies are rapidly becoming the standard for molecular assays and represent huge potential value to the practice of oncology. However, many challenges exist in the transition of these technologies from research application to clinical practice. This review discusses the value of NGS in detecting mutations, copy number changes and RNA quantification and their applications in oncology, the challenges for adoption and the relevant steps that are needed for translating this potential to routine practice.
    Molecular oncology 05/2013; 9. DOI:10.1016/j.molonc.2013.04.008 · 5.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: AIM: The vascular endothelial growth factor (VEGF) or its family might play role in tumor-related angiogenesis in gastrointestinal stromal tumors (GIST), thereby affecting the prognosis. Accordingly, the present study analyzed the impact of VEGF and VEGF receptor-2 (VEGFR-2) gene polymorphisms on the prognosis for GIST patients. METHODS: In all, 213 consecutive patients with GIST from five medical centers were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tumor tissue, and four VEGF (-2578C/A, -1498C/T, -634G/C, and +936C/T) and one VEGFR-2 (+1416A/T) gene polymorphisms were determined using a Sequenom MassARRAY system. RESULTS: With a median follow up of 18.4 months, the estimated 5-year relapse-free survival and overall survival rates were 70 and 87%, respectively. In a multivariate analysis including age, sex, primary site of disease, pathology and risk stratification, no significant association was observed between the polymorphism of the VEGF and VEGFR-2 genes and survival. CONCLUSION: None of the five VEGF and VEGFR-2 gene polymorphisms investigated in this study was found to be an independent prognostic marker for Korean patients with surgically resected GIST. However, further studies on a larger scale are warranted to clarify the role of VEGF and VEGFR gene polymorphisms as a prognostic biomarker for GIST patients.
    Asia-Pacific Journal of Clinical Oncology 04/2013; 10(2). DOI:10.1111/ajco.12068 · 1.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lung cancer is the leading cause of cancer-related mortality. Small cell lung cancer (SCLC) accounted for 12.95% of all lung cancer histological types in 2002. Despite trends toward modest improvement in survival, the outcome remains extremely poor. Chemotherapy is the cornerstone of treatment in SCLC. More than two-thirds of patients who succumb to lung cancer in the United States are over 65 years old. Elderly patients tolerate chemotherapy poorly and need novel therapeutic agents. Targeted drugs have less toxicity than chemotherapy drugs, but no targeted agents have been approved for use in the treatment of SCLC patients to date. Certain new targeted agents, including gefitinib, bevacizumab and Bcl-2 inhibitors, offer a promise of improved outcomes, however negative results are more commonly reported than positive. This review focuses on targeted therapies in SCLC.
    Oncology letters 01/2013; 5(1):3-11. DOI:10.3892/ol.2012.791 · 0.99 Impact Factor