The lancet oncology
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The lancet oncology · Sep 2014
Randomized Controlled Trial Comparative StudySafety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study.
Patients with non-small-cell lung cancer (NSCLC) and ALK rearrangements generally have a progression-free survival of 8-11 months while on treatment with the ALK inhibitor crizotinib. However, resistance inevitably develops, with the brain a common site of progression. More potent ALK inhibitors with consistently demonstrable CNS activity and good tolerability are needed urgently. Alectinib is a novel, highly selective, and potent ALK inhibitor that has shown clinical activity in patients with crizotinib-naive ALK-rearranged NSCLC. We did a phase 1/2 study of alectinib to establish the recommended phase 2 dose of the drug and examine its activity in patients resistant or intolerant to crizotinib. ⋯ Chugai Pharmaceuticals, F Hoffmann La-Roche.
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The lancet oncology · Sep 2014
Randomized Controlled Trial Comparative StudyActive monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial.
Prostate cancer is a major public health problem with considerable uncertainties about the effectiveness of population screening and treatment options. We report the study design, participant sociodemographic and clinical characteristics, and the initial results of the testing and diagnostic phase of the Prostate testing for cancer and Treatment (ProtecT) trial, which aims to investigate the effectiveness of treatments for localised prostate cancer. ⋯ UK National Institute for Health Research Health Technology Assessment Programme.
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The lancet oncology · Sep 2014
ReviewCombination of stereotactic ablative body radiation with targeted therapies.
Recent advances allow safe and effective delivery of ablative doses of radiation with stereotactic precision to tumours, resulting in very high levels of tumour control. Parallel advances in the understanding of tumour biology enable delivery of systemic drugs that selectively antagonise biological pathways in the tumour and surrounding microenvironment. ⋯ In this Review we summarise the biological rationale and clinical data for both sterotactic ablative radiotherapy (SABR) and targeted therapies, and the emerging experience with combination of these treatments. We describe potential pathways of cooperation in both tumour and normal tissue between SABR and targeted drugs, and, because fatal toxicities have been reported, we outline clinical precautions.
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The lancet oncology · Sep 2014
ReviewPathogenesis, diagnosis, and treatment of composite lymphomas.
In rare instances, two distinct lymphomas concurrently occur in a patient. Such composite lymphomas can be combinations of two non-Hodgkin lymphomas or a combination of a non-Hodgkin lymphoma and a Hodgkin's lymphoma. Composite lymphomas pose a particular diagnostic challenge, and there are currently no agreed standards for treatment. ⋯ This finding suggests a scenario in which the common premalignant precursor had acquired shared transforming events, and the two distinct lymphomas developed from descendants of that precursor after acquiring additional separate transforming events. Findings from molecular studies support this notion. Hence, clonally related composite lymphomas are elegant models to study the multistep transformation process in lymphomagenesis.
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The lancet oncology · Sep 2014
Randomized Controlled Trial Comparative StudyShort-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR): an open-label, randomised, phase 3 factorial trial.
We investigated whether 18 months of androgen suppression plus radiotherapy, with or without 18 months of zoledronic acid, is more effective than 6 months of neoadjuvant androgen suppression plus radiotherapy with or without zoledronic acid. ⋯ National Health and Medical Research Council of Australia, Novartis Pharmaceuticals Australia, Abbott Pharmaceuticals Australia, New Zealand Health Research Council, New Zealand Cancer Society, University of Newcastle (Australia), Calvary Health Care (Calvary Mater Newcastle Radiation Oncology Fund), Hunter Medical Research Institute, Maitland Cancer Appeal, Cancer Standards Institute New Zealand.