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The efficacy of cetuximab (Erbitux) plus chemoradiation in patients with locally advanced non-small-cell lung cancer does not appear to vary with the tumor's epidermal growth factor receptor expression, according to preliminary results of a phase II trial

A 68-year-old man with a history of small-cell lung cancer with bony metastases was admitted with diarrhea. The patient had completed chemotherapy one week earlier with cisplatin and etoposide, along with radiation therapy, and irinotecan (Camptosar). The patient was found to be neutropenic.

Radiation therapy (RT) is an important treatment modality for multiple thoracic malignancies. Incidental irradiation of the lungs, which are particularly susceptible to injury, is unavoidable and often dose-limiting. The most radiosensitive subunit of the lung is the alveolar/capillary complex, and RT-induced lung injury is often described as diffuse alveolar damage. Reactive oxygen species generated by RT are directly toxic to parenchymal cells and initiate a cascade of molecular events that alter the cytokine milieu of the microenvironment, creating a self-sustaining cycle of inflammation and chronic oxidative stress. Replacement of normal lung parenchyma by fibrosis is the culminating event. Depending on the dose and volume of lung irradiated, acute radiation pneumonitis may develop, characterized by dry cough and dyspnea. Fibrosis of the lung, which can also cause dyspnea, is the late complication. Imaging studies and pulmonary function tests can be used to quantify the extent of lung injury. While strict dose-volume constraints to minimize the risk of injury are difficult to impose, substantial data support some general guidelines. New modalities such as intensity-modulated radiation therapy and stereotactic body radiation therapy provide new treatment options but also pose new challenges in safely delivering thoracic RT.

Radiation therapy (RT) is an important treatment modality for multiple thoracic malignancies. Incidental irradiation of the lungs, which are particularly susceptible to injury, is unavoidable and often dose-limiting. The most radiosensitive subunit of the lung is the alveolar/capillary complex, and RT-induced lung injury is often described as diffuse alveolar damage. Reactive oxygen species generated by RT are directly toxic to parenchymal cells and initiate a cascade of molecular events that alter the cytokine milieu of the microenvironment, creating a self-sustaining cycle of inflammation and chronic oxidative stress. Replacement of normal lung parenchyma by fibrosis is the culminating event. Depending on the dose and volume of lung irradiated, acute radiation pneumonitis may develop, characterized by dry cough and dyspnea. Fibrosis of the lung, which can also cause dyspnea, is the late complication. Imaging studies and pulmonary function tests can be used to quantify the extent of lung injury. While strict dose-volume constraints to minimize the risk of injury are difficult to impose, substantial data support some general guidelines. New modalities such as intensity-modulated radiation therapy and stereotactic body radiation therapy provide new treatment options but also pose new challenges in safely delivering thoracic RT.

Patients with locally advanced non-small-cell lung cancer and a good performance status have better overall survival and a lower risk of local-regional progression if they receive concomitant chemoradiation instead of sequential chemoradiation, according to a meta-analysis from the NSCLC Collaborative Group presented at this year's ASTRO meeting

Erlotinib (Tarceva) is a human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor initially approved by the US Food and Drug Administration for the treatment of patients with locally advanced or metastatic non–small-cell lung cancer after failure of at least one prior chemotherapy regimen. In this report, we present the pivotal study that led to the approval of erlotinib in combination with gemcitabine (Gemzar) in patients with locally advanced/metastatic chemonaive pancreatic cancer patients. The combination demonstrated a statistically significant increase in overall survival accompanied by an increase in toxicity. Physicians and patients now have a new option for the treatment of locally advanced/metastatic adenocarcinoma of the pancreas.

A significant proportion of patients with non-small cell lung cancer (NSCLC) present with locally advanced, unresectable disease. For the most part, fit patients with this diagnosis are treated with combined-modality therapy. Relatively few are rendered resectable. Over the past two decades, combination chemotherapy and radiation, preferably concurrent chemoradiation, has emerged as the standard of care. However, survival gains have been offset, to some extent, by local, normal-tissue, in-field toxicity, particularly esophagitis and pneumonitis.

Erlotinib (Tarceva) is a human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor initially approved by the US Food and Drug Administration for the treatment of patients with locally advanced or metastatic non–small-cell lung cancer after failure of at least one prior chemotherapy regimen. In this report, we present the pivotal study that led to the approval of erlotinib in combination with gemcitabine (Gemzar) in patients with locally advanced/metastatic chemonaive pancreatic cancer patients. The combination demonstrated a statistically significant increase in overall survival accompanied by an increase in toxicity. Physicians and patients now have a new option for the treatment of locally advanced/metastatic adenocarcinoma of the pancreas.

Erlotinib (Tarceva) is a human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor initially approved by the US Food and Drug Administration for the treatment of patients with locally advanced or metastatic non–small-cell lung cancer after failure of at least one prior chemotherapy regimen. In this report, we present the pivotal study that led to the approval of erlotinib in combination with gemcitabine (Gemzar) in patients with locally advanced/metastatic chemonaive pancreatic cancer patients. The combination demonstrated a statistically significant increase in overall survival accompanied by an increase in toxicity. Physicians and patients now have a new option for the treatment of locally advanced/metastatic adenocarcinoma of the pancreas.

Angiogenesis is a critical requirement for malignant growth, invasion, and metastases. Agents interfering with angiogenesis have shown efficacy in the treatment of a number of solid tumors, such as metastatic colorectal cancer, non–small-cell lung cancer, and renal cell cancer, and are being studied in many more. Each of the three agents currently approved by the US Food and Drug Administration-bevacizumab (Avastin), sunitinib (Sutent), and sorafenib (Nexavar)-offer challenges to nurses, in terms of assessment and management of toxicity, and to their patients as well: learning and integrating self-care strategies, such as self-assessment and self-administration (for sorafenib and sunitinib). This article reviews the recommended dosing, drug interactions, potential side effects, and management strategies for these three agents. Other agents that have antiangiogenesis properties, such as the epidermal growth factor inhibitors, the mTOR inhibitors, bortezomib, and thalidomide will not be addressed.

A growing number of novel antiangiogenic agents are entering clinical trials to study their clinical safety and efficacy. A few, such as bevacizumab (Avastin), sorafenib (Nexavar), and sunitinib (Sutent), have received US Food and Drug Administration approval and are already in widespread clinical use. As knowledge about the intricacies of intracellular signaling within multiple tumor types expands, agents with the capacity to impact these pathways are being incorporated into additional clinical trials alone and in combination with other targeted and/or traditional antineoplastic agents. Early clinical trials have focused on highly vascular tumor types, as well as those known to significantly overexpress the VEGF (vascular endothelial growth factor) receptor family. This article aims to review the status of antiangiogenic therapy in selected tumor types and discuss areas for further research.