ASCO Provisional Clinical Opinion: Epidermal Growth Factor Receptor Mutation Testing in Practice.

ASCO has recently provided guidance on emerging data on EGFR testing for the purpose of selecting first-line therapy for persons with advanced NSCLC through its Provisional Clinical Opinion.

American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) Mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy.

Purpose: An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to ASCO's membership following publication or presentation of potentially practice-changing data from major studies. This PCO addresses the clinical utility of using epidermal growth factor receptor (EGFR) mutation testing for patients with advanced non-small-cell lung cancer (NSCLC) to predict the benefit of taking a first-line EGFR tyrosine kinase inhibitor (TKI).

Clinical Context: Patients with EGFR-mutated NSCLC have a significantly higher rate of partial responses to the EGFR TKIs gefitinib and erlotinib.

Randomized phase II study of pulse erlotinib before or after carboplatin and paclitaxel in current or former smokers with advanced non-small-cell lung cancer.

Purpose: A prior study demonstrated that addition of continuous daily erlotinib fails to improve response rate or survival in non-small-cell lung cancer (NSCLC) patients treated with carboplatin and paclitaxel. However, preclinical data support the hypothesis that intermittent administration of erlotinib before or after chemotherapy may improve efficacy. We tested this hypothesis in patients with advanced NSCLC.

Targeting Lewis Y (Le(y)) in small cell lung cancer with a humanized monoclonal antibody, hu3S193: a pilot trial testing two dose levels.

Introduction: Lewis Y (Le(y)) is a blood group antigen with robust expression on the surface of epithelial tumors, including small cell lung cancer (SCLC), making it a potential target for antibody-based immunotherapy. 3S193, an immunoglobulin G3 monoclonal antibody, has demonstrated superior specificity, affinity, and cytotoxicity over other anti-Le(y) antibodies. A phase I trial of humanized 3S193 (hu3S193) with dosing up to 40 mg/m2 demonstrated tumor targeting without serious toxicities or the development of human anti-human antibodies.

Prospective assessment of discontinuation and reinitiation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or gefitinib followed by the addition of everolimus.

Purpose: Ten percent of U.S. patients with non-small cell lung cancer experience partial radiographic responses to erlotinib or gefitinib.

Phase 1 trial of everolimus and gefitinib in patients with advanced nonsmall-cell lung cancer.

Background: Preclinical studies have demonstrated that the inhibition of the PI3K/Akt/mTOR pathway restores gefitinib sensitivity in resistant cancer cell lines. A phase 1 study was conducted of the combination of everolimus, an mTOR inhibitor, and gefitinib to determine a daily dose of everolimus with gefitinib in patients with advanced nonsmall-cell lung cancer (NSCLC).

Methods: Oral everolimus and gefitinib were both administered daily to patients with progressive NSCLC.

Mitomycin-C/5-fluorouracil/leucovorin and hyperfractionated radiation therapy for rectal carcinoma: a phase II study with long-term follow-up.

Purpose: Preoperative chemotherapy followed by surgery and adjuvant chemotherapy is a standard treatment for most patients with rectal cancer. We aimed to determine efficacy and tolerability of preoperative mitomycin, fluorouracil (5-FU), and leucovorin (LV) concurrent with hyperfractionated radiation therapy (RT) followed by surgery and adjuvant chemotherapy.

Patients And Methods: Patients with clinical stage II/III disease were treated with mitomycin 10 mg/m(2) on day 1, continuous venous infusion 5-FU 600 mg/m(2) per day for 96 hours, and oral LV 25 mg every 6 hours on days 1-5.

A phase I/II study of weekly high-dose erlotinib in previously treated patients with nonsmall cell lung cancer.

Background: Preclinical studies have suggested that erlotinib at high doses may inhibit additional sites downstream of the epidermal growth factor receptor (EGFR), resulting in greater antitumor efficacy. The objective of this study was to determine the tolerability and efficacy of high-dose erlotinib administered on a weekly schedule to patients with advanced nonsmall cell lung cancer (NSCLC).

Methods: The authors conducted a Phase I/II trial of weekly erlotinib in patients with progressive NSCLC who had received previous chemotherapy.

Advances in cytotoxic chemotherapy for the treatment of metastatic or recurrent non-small cell lung cancer.

Improvements in drug development and clinical trial design have resulted in a wider range of treatment options for patients with advanced non-small cell lung cancer (NSCLC). Combination chemotherapy is the standard of care for medically fit patients. A variety of chemotherapeutic doublets, including nonplatinum combinations, with similar clinical activity are now available, allowing oncologists to match acceptable toxicity profiles to individual patients' comorbidities and preferences.

High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to gefitinib.

Background: Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor that induces an early and dramatic response in 10% of patients with advanced nonsmall cell lung carcinoma (NSCLC). Long- term outcome and patterns of disease recurrence after response have not been described.

Methods: The authors evaluated 139 patients with NSCLC treated with gefitinib at Memorial Sloan-Kettering Cancer Center (New York, NY) between 1998 and 2002.

Prompt control of bronchorrhea in patients with bronchioloalveolar carcinoma treated with gefitinib (Iressa).

Bronchorrhea is a condition in which voluminous sputum is produced daily, typically seen with bronchioloalveolar cell carcinoma (BAC). Unless the underlying cancer can be controlled, bronchorrhea causes substantial symptomatic distress. We report two cases of bronchorrhea associated with advanced BAC successfully treated with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib.