Journal of clinical oncology : official journal of the American Society of Clinical Oncology
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Review
Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer.
The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor of the ErbB family that is abnormally activated in many epithelial tumors. Receptor activation leads to recruitment and phosphorylation of several downstream intracellular substrates, leading to mitogenic signaling and other tumor-promoting cellular activities. In human tumors, receptor overexpression correlates with a more aggressive clinical course. ⋯ Although antitumor activity is significant, responses have been seen in only a minority of the patients treated. In some clinical trials, anti-EGFR agents enhanced the effects of conventional chemotherapy and radiation therapy. Ongoing research efforts are directed at the selection of patients with EGFR-dependent tumors, identification of the differences among the various classes of agents, and new clinical development strategies.
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A greater understanding of cancer biology and major advances in biotechnology have resulted in the identification of a plethora of rationally designed, target-based anticancer therapeutics, particularly those that inhibit malignant-cell signal transduction, ushering in new therapeutic opportunities and extraordinary developmental challenges. Because these agents seem to principally target malignant cells, it is expected that they will produce less toxicity at clinically effective doses than nonspecific cytotoxic agents. The innate complexity of signaling networks, which have redundant relay systems that confer robustness, adaptability, and signaling diversity, also decreases the probability that any single therapeutic manipulation against any specific signaling element will be highly successful when used alone, particularly in patients with solid malignancies that have multiple relevant signaling aberrations. ⋯ Furthermore, the results of preclinical and early clinical studies indicate that dose-toxicity relationships are not likely to be as steep as with nonspecific cytotoxic agents. Therefore, both regulatory and clinical practice end points, such as time to disease progression, disease-related symptoms, and quality of life, which are generally considered secondary for cytotoxic agents, may evolve into primary end points. The cumulative results of developmental evaluations to date indicate that the development, evaluation, and general clinical use of rationally designed, target-based anticancer therapeutics will require a radical departure from traditional paradigms to exploit the full potential of these new therapies.
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The introduction of imatinib, a specific inhibitor of the Bcr-Abl tyrosine kinase, has dramatically changed the management of chronic myeloid leukemia (CML). More than 10,000 patients worldwide have been treated with imatinib in clinical trials, and a large body of information has accumulated about the use of this drug. The purpose of this article is to review practical guidelines in regard to optimal dosing, monitoring, managing common side effects such as myelosuppression, and potential drug interactions. The treatment recommendations are intended to optimize therapy with imatinib while taking into account a patient's specific circumstances.
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Review
Identifying potential indicators of the quality of end-of-life cancer care from administrative data.
To explore potential indicators of the quality of end-of-life services for cancer patients that could be monitored using existing administrative data. ⋯ Several promising claims-based quality indicators were identified that, if found to be valid and reliable within data systems, could be useful in identifying health-care systems in need of improving end-of-life services.
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The delivery of quality care to all patients with cancer has been named as a national priority within the American health care system. This article addresses the issues critical to case identification in cancer quality measurement and recommends possible strategies for accurately identifying a population of cancer patients. ⋯ Using an existing data collection system staffed by skilled data collectors and managers should result in substantially more accurate and timely data. Registry officials and the government agencies that provide their support should be encouraged to adopt quality-of-care analyses as an important purpose of the registry system and to enhance their capacity to rapidly ascertain cases, collect the appropriate identifying information needed for patient contact, and verify stage at diagnosis. In order to meet the growing demand for timely, accurate information about quality of care, registries are likely to require additional support so they can enhance their capacity to rapidly ascertain cases, collect the appropriate identifying information needed for patient contact, and verify stage at diagnosis.