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Cetuximab (Erbitux, IMC-C225, ImClone Systems Incorporated, New York, NY) is a monoclonal antibody targeted to the epidermal growth factor receptor. Expression of the epidermal growth factor receptor is associated with disease progression, poor survival, poor response to therapy, and the development of resistance to therapy in many solid tumors. Cetuximab blocks the binding of natural ligands to the epidermal growth factor receptor, thus inhibiting oncogenic processes associated with its activation. Infusion reactions, acneform skin rash, and nail disorder are the most clinically relevant adverse events observed. Because infusion reactions can be life threatening when severe, nurses must administer prophylactic treatment with an H1 antagonist prior to infusion and actively manage cetuximab-related infusion reactions when they occur. Management of infusion reactions typically includes vigilant patient monitoring, appropriate medical supervision, readily available resources for the treatment of infusion reactions, and initiation of institution- or practice-specific protocols when necessary. Acneform skin rash is the most common adverse event, but severe (grade 3 or 4) rash requiring interruption of treatment is not common. Topical and systemic antibiotic therapies may be administered to reduce symptoms. Nail disorder typically is mild to moderate and is observed infrequently; this also may be treated with systemic and topical antibiotics. Overall, the safety profile of cetuximab is favorable compared to that typically seen with chemotherapeutic agents. The acneform skin rash and nail disorder, which may affect quality of life, rarely threaten the general well-being of patients and typically are manageable.

BACKGROUND: Patients with advanced non–small-cell lung cancer (NSCLC) and poor performance status (PS) are often excluded from trials. Gefitinib is a safe oral agent that may benefit these patients. PATIENTS AND METHODS: Seventy-two patients with poor PS and advanced NSCLC were enrolled onto this study of gefitinib 250 mg per day given orally until disease progression, with evaluation at 8 weeks. Eligible patients had no previous chemotherapy, an Eastern Cooperative Oncology Group PS of 2/3, and stage IIIB/IV NSCLC. Quality of life (QOL) and symptom response (SR) scores were calculated using the Functional Assessment of Cancer–Lung questionnaire. Patient characteristics included a median age of 75 years; PS of 2/3; and bronchoalveolar (n = 3), adenocarcinoma (n = 29), squamous cell (n = 21), large-cell (n = 11), and unspecified histology (n = 6). Mean treatment duration was 4 months (range, 3 days to 18 months), and median duration of follow-up was 12 months. Grade 3/4 toxicities included rash and diarrhea. RESULTS: Among 70 patients assessed for response, there were 3 partial responses (4%), 32 patients with stable disease (46%), and 18 with progressive disease (26%). Median progression-free survival (PFS) and overall survival (OS) were 3.7 months and 6.3 months, respectively. Six-month and 1-year PFS and OS rates were 35% and 21% and 50% and 24%, respectively. Eighty-two percent and 48% of patients reported improvements or no change in QOL and SR, respectively. CONCLUSION: Gefitinib demonstrates modest efficacy and is well tolerated as initial therapy in advanced NSCLC for patients with poor PS.

Objectives: To provide an overview of the clinical development of ZD1839 and other epidermal growth factor receptor (EGFR) inhibitors in the treatment of advanced non-small cell lung cancer (NSCLC). Data Sources: Research articles and abstracts. Conclusions: Increased understanding of cancer biology has led to the development of multiple targeted agents to evaluate clinically in the treatment of various cancers. The EGFR inhibitors appear promising in the treatment of NSCLC. ZD1839 has shown activity and symptom and quality-of-life improvements in two large phase II trials. Ongoing and future trials will continue to explore the optimal use of ZD1839 and other EGFR inhibitors in the treatment of NSCLC. Implications for Nursing Practice: Several investigational EGFR inhibitors are likely to become commercially available over the next few years. Nurses should be knowledgeable regarding these agents to provide appropriate patient and family education and to assure safe drug delivery.

Despite treatment advances over the past decade, long-term survival for patients with non-small cell lung cancer (NSCLC) remains poor, and treatment options available after second-line therapy are limited. Increased understanding of cancer biology has led to the identification of several potential targets for treatment. The epidermal growth factor receptor (EGFR) belongs to a family of plasma membrane receptor tyrosine kinases that controls many important cellular functions, from growth and proliferation to cell death. This receptor is a particularly promising therapeutic target because it often is overexpressed in patients with NSCLC and has been implicated in the pathogenesis as well as the proliferation, invasion, and metastasis of lung cancer and other malignancies. New agents developed to inhibit EGFR function include small-molecule tyrosine kinase inhibitors, monoclonal antibodies to EGFR, and pan-EGFR inhibitors. Completed and ongoing clinical trials have shown that EGFR inhibitors have remarkable efficacy for patients with relapsed NSCLC. Among these, two phase 2 trials have shown that ZD1839 is effective when used as monotherapy. The response rates are comparable with those for docetaxel given in the second-line setting. Another phase 2 trial has shown that OSI-774 is effective in the same setting. Data from phase 3 trials indicate that adding an EGFR tyrosine kinase inhibitor to chemotherapy does not provide an additional survival benefit, as compared with standard chemotherapy alone for first-line treatment of NSCLC. It appears that EGFR tyrosine kinase inhibitors are safe and well tolerated by patients with cancer. Further studies will elucidate how these new agents can best be used for NSCLC and other tumor types.