The oncologist
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Angiogenesis, or the formation of new capillary blood vessels, occurs primarily during human development and reproduction; however, aberrant regulation of angiogenesis is also a fundamental process found in several pathologic conditions, including cancer. As a process required for invasion and metastasis, tumor angiogenesis constitutes an important point of control of cancer progression. Although not yet completely understood, the complex process of tumor angiogenesis involves highly regulated orchestration of multiple signaling pathways. The proangiogenic signaling molecule vascular endothelial growth factor (VEGF) and its cognate receptor (VEGF receptor 2 [VEGFR-2]) play a central role in angiogenesis and often are highly expressed in human cancers, and initial clinical efforts to develop antiangiogenic treatments focused largely on inhibiting VEGF/VEGFR signaling. Such approaches, however, often lead to transient responses and further disease progression because angiogenesis is regulated by multiple pathways that are able to compensate for each other when single pathways are inhibited. The platelet-derived growth factor (PDGF) and PDGF receptor (PDGFR) and fibroblast growth factor (FGF) and FGF receptor (FGFR) pathways, for example, provide potential escape mechanisms from anti-VEGF/VEGFR therapy that could facilitate resumption of tumor growth. Accordingly, more recent treatments have focused on inhibiting multiple signaling pathways simultaneously. This comprehensive review discusses the limitations of inhibiting VEGF signaling alone as an antiangiogenic strategy, the importance of other angiogenic pathways including PDGF/PDGFR and FGF/FGFR, and the novel current and emerging agents that target multiple angiogenic pathways for the treatment of advanced solid tumors. ⋯ Significant advances in cancer treatment have been achieved with the development of antiangiogenic agents, the majority of which have focused on inhibition of the vascular endothelial growth factor (VEGF) pathway. VEGF targeting alone, however, has not proven to be as efficacious as originally hoped, and it is increasingly clear that there are many interconnected and compensatory pathways that can overcome VEGF-targeted inhibition of angiogenesis. Maximizing the potential of antiangiogenic therapy is likely to require a broader therapeutic approach using a new generation of multitargeted antiangiogenic agents.
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Guidance and exploratory evidence indicate that the type of endpoints and the magnitude of their outcome can define a therapy's clinical activity; however, little empirical evidence relates specific endpoint properties with regulatory outcomes. ⋯ Regulatory decisions made by the European Medicines Agency determine which new medicines will be available to European prescribers and for which therapeutic indications. Regulatory success or failure can be influenced by many factors. This study assessed three key properties of endpoints used in preauthorization trials (type of endpoint [hard/surrogate], magnitude of endpoint outcome, and its statistical significance) and whether they are associated with a positive regulatory outcome. Clinicians can use these properties, which are described in the publicly available European public assessment reports, to help guide their understanding of the clinical effect of new oncologic therapies.
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Adherence to adjuvant endocrine therapy (ET) influences breast cancer survival. Because ET side effects are frequently cited as reasons for nonadherence, understanding how perceptions and motivations in relation to ET are associated with symptom attribution can help promote timely symptom management. ⋯ Many breast cancer survivors on endocrine therapy (ET) experience a range of side effects while taking ET. Targeting potentially modifiable factors associated with attributing a greater number of symptoms to ET, including perceived need for ET, concerns about long-term ET use, negative emotions toward ET, and symptoms of anxiety and depression, may reduce symptom burden and improve quality of life.
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In this prospective study, we determined the frequency of opioid-related chemical coping among advanced cancer patients, as diagnosed by palliative medicine specialists. We also determined predictors for chemical coping and the concordance between the physician's diagnosis and documentation in the medical records. ⋯ Cancer pain is a multidimensional symptom for which opioids are the mainstay of treatment. However, opioids can have a double effect resulting in drug-seeking behaviors. Chemical coping occurs when a patient uses opioids in a nonprescribed way to cope with various stressful events. This can lead to misuse of opioids and complications including neurotoxicities, respiratory depression, and death. Proper diagnosis and documentation is needed to ensure proper management of pain and to avoid unnecessary harm. The findings of this study suggest that ∼18% of advanced cancer patients seen by a palliative care service were diagnosed as chemical coping, but only 4% were documented in the medical records.
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The 5-year oncologic outcomes from the trial regimen were excellent. However, the neoadjuvant and surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy.Due to the lack of an improvement in the pathologic complete response rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study. ⋯ Despite the path-CR primary endpoint of this trial not being reached, the 5-year OS and recurrence-free survival rates were excellent. However, the neoadjuvant and surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy. Because of the lack of an improvement in the path-CR rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study.