The lancet oncology
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The lancet oncology · Oct 2008
Review Meta AnalysisAssessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer.
Somatic mutations of the k-RAS oncogene have been assessed as a mechanism of de-novo resistance to epidermal growth factor receptor (EGFR) tyrosine-kinase inhibition in patients with non-small-cell lung cancer (NSCLC), and to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer (mCRC). The aim of this systematic review and meta-analysis was to assess if k-RAS mutations represent a candidate predictive biomarker for anti-EGFR-targeted therapeutic strategies in mCRC and NSCLC. ⋯ This analysis provides empirical evidence that k-RAS mutations are highly specific negative predictors of response (de-novo resistance) to single-agent EGFR TKIs in advanced NSCLC; and similarly to anti-EGFR monoclonal antibodies alone or in combination with chemotherapy in patients with mCRC. The low sensitivity and relatively high -LR of k-RAS mutations for determining non-responsiveness clearly shows that additional mechanisms of resistance to EGFR inhibitors exist.
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The lancet oncology · Oct 2008
Randomized Controlled Trial Comparative StudyEffects of anastrozole on cognitive performance in postmenopausal women: a randomised, double-blind chemoprevention trial (IBIS II).
Mild cognitive impairments have been recorded in cross-sectional studies of women with breast cancer receiving endocrine treatment. More comprehensive studies were warranted because aromatase inhibitors are being used increasingly in both chemoprevention and adjuvant settings. We report findings from the cognitive subprotocol of the International Breast Intervention Study (IBIS II), a double-blind placebo-controlled trial of anastrozole in postmenopausal women at high risk of developing breast cancer. We aimed to study and compare the effect of anastrozole versus placebo on memory and attention in these women. ⋯ Cancer Research UK, London, UK (grant numbers C6280/A3162 and C6280/A6764).
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The lancet oncology · Oct 2008
Use of lipoteichoic acid-T for pleurodesis in malignant pleural effusion: a phase I toxicity and dose-escalation study.
Bacterial infection of the pleural space often causes adherence of the pleural membranes by fibrous tissue, probably mediated by inflammation initiated by bacterial cell-wall motifs, including lipoteichoic acid-T (LTA-T). We postulated that therapeutically administered LTA-T might produce a similar effect, achieving control of malignant pleural effusion (pleurodesis). ⋯ The toxic effects of intrapleural LTA-T seem to be mild and favourable when compared with the toxicity profiles of standard pleurodesis agents. There is early evidence of LTA-T-induced pleurodesis efficacy, suggesting that this might be a viable therapeutic strategy for the control of malignant pleural effusion.
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The lancet oncology · Oct 2008
Eligibility of patients with brain metastases for phase I trials: time for a rethink?
Since the inception of phase I clinical trials in cancer, patients with symptomatic brain metastases have commonly been excluded from participation because of a poor outlook. However, patients with asymptomatic brain metastases pose an increasingly frequent challenge for clinicians: more sensitive brain imaging can identify clinically silent brain metastases; frequency of detection might have increased because of changes in the natural history of many tumour types as a result of more effective systemic treatment; and routine brain imaging as a screening procedure before entry into a clinical trial can show lesions which are of questionable clinical importance, but which frequently preclude trial enrolment. ⋯ We think that a subset of patients with asymptomatic brain metastases might be appropriately entered into phase I trials, and we present our approach for their stratification. As a consequence, patients might have increased access to experimental treatments and thus effective interventions for brain metastases might be developed more promptly.
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Apoptosis is a fundamental process in the development and maintenance of multicellular organisms and its regulation is commonly disrupted in human cancers. In vitro and in vivo, effective treatment of cancer with radiotherapy or anticancer drugs (or both) is frequently associated with increased markers of apoptosis. ⋯ With increased understanding of the regulatory and effector molecules of apoptosis new drugs have been developed that might manipulate the apoptotic balance in cancer cells in favour of cell death. This Review summarises the rationale for direct manipulation of various elements of apoptosis and describes agents that are currently under investigation in early-phase clinical trials in many different cancer types.