Seminars in oncology
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Seminars in oncology · Apr 2005
ReviewSedation for the relief of refractory symptoms in the imminently dying: a fine intentional line.
There is a continuum of the goals of comfort and function in palliative care that begins with comfort and function being equal priorities and sedation being unacceptable. As disease progresses, the goals and preferences of the patient turn to coping with the loss of function caused by the disease and acceptance of unintentional sedation from the disease, its therapies, or symptom relief interventions. ⋯ Extraordinary sedation with continuous infusions of midazolam, thiopental, and propofol can relieve refractory symptoms in most patients in their final days of life. Palliative care clinicians should become comfortable with the ethical justification and technical expertise needed to provide this essential, extraordinary care to the small but deserving number of patients in whom routine and infrequent sedation does not adequately relieve their suffering.
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Seminars in oncology · Apr 2005
Randomized Controlled Trial Clinical TrialMutagen sensitivity may predict lung protection by amifostine for patients with locally advanced non-small cell lung cancer treated by chemoradiotherapy.
Amifostine (AMF) has been shown to protect some normal tissues from acute effects of radiation therapy +/- chemotherapy. We enrolled 62 patients in a randomized study investigating the efficacy of AMF: 31 had concurrent chemoradiation for non-small cell lung cancer and 31 had the same treatment + AMF. AMF reduced the frequency and severity of esophagitis, pneumonitis, and neutropenic fever. ⋯ Higher MS was associated with shorter distant metastasis-free survival and more frequent grade 3/4 lung fibrosis. AMF reduced the incidence of grade 3/4 lung fibrosis among higher MS. These data suggest that MS might help identify subgroups of patients who could receive more benefit from AMF with respect to lung damage.
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Seminars in oncology · Apr 2005
ReviewInhibition of the epidermal growth factor receptor in combined modality treatment for locally advanced non-small cell lung cancer.
Epidermal growth factor receptor 1 (EGFR 1 ) is a 170-kd glycoprotein that plays many roles in the growth of non-small cell lung cancer (NSCLC). There are four known receptors in the EGFR family. Binding of a ligand such as epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) causes EGFR to undergo a conformational change leading to autophosphorylation of EGFR and activation of the EGFR growth factor pathway. ⋯ Cancer and Leukemia Group B 30106 and a multi-institutional Australian phase I trial have shown that gefitinib can be added to concurrent chemoradiotherapy for stage III NSCLC without excessive toxicity. A phase I trial at the University of Chicago (Chicago, IL) has evaluated erlotinib with concurrent chemoradiotherapy in stage III NSCLC. Radiation Therapy Oncology Group 0324 is an on-going phase II trial studying cetuximab and concurrent chemoradiotherapy in stage III NSCLC.
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Current therapeutic approaches for lung cancer favor treatment intensification, with the presumption that dose-intense chemotherapy regimens and/or higher radiation therapy (RT) doses or novel fractionation schemes will result in increased patient survival. Also, the trend for non-operative therapy has favored concurrent over sequential regimens. The incidence of severe acute esophagitis in patients treated for lung cancer with standard (once daily) RT alone is 1.3%, and induction chemotherapy increases the risk of severe acute esophagitis slightly over that of standard RT alone. ⋯ The Radiation Therapy Oncology Group (RTOG) conducted a large phase III, randomized study RTOG 98-01 examining chemoRT with or without the amifostine (Ethyol; MedImmune, Inc, Gaithersburg, MD), a cyto- and radioprotectant in locally advanced non-small cell lung cancer (n = 243). While amifostine did not significantly reduce severe esophagitis based on National Cancer Institute Common Toxicity Criteria and weekly physician dysphagia logs, swallowing dysfunction over time (based on patient diaries, the equivalent of Esophagitis Index) was significantly lower in the amifostine arm ( P = .03). Therefore, significant progress has been accomplished in our understanding of the basis of esophageal injury resulting from thoracic RT, and future effort may find other effective strategies to either minimize or eliminate esophagitis.