epidermal-growth-factor and Carcinoma--Bronchogenic

Gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, induces radiographic regressions and symptomatic improvement in patients with non-small-cell lung cancer (NSCLC). Phase II trials suggested female sex and adenocarcinoma were associated with response. We undertook this analysis to identify additional clinical and pathologic features associated with sensitivity to gefitinib.. We reviewed medical records, pathologic material, and imaging studies of all 139 NSCLC patients treated on one of three consecutive studies of gefitinib monotherapy performed at our institution. We identified patients experiencing a major objective response and compared their clinical and pathologic features with the others. Univariate and multivariable analyses were performed on potential predictive features associated with sensitivity to gefitinib.. Of 139 patients, 21 (15%; 95% CI, 9% to 21%), experienced a partial radiographic response. Variables identified as significant in univariate analysis included adenocarcinoma versus other NSCLC (19% v 0%; P=.004), adenocarcinoma with bronchioloalveolar features versus other adenocarcinomas (38% v 14%; P<.001), never smoker status versus former/current (36% v 8%; P<.001), and Karnofsky performance status > or =80% versus < or =70% (22% v 8%; P=.03). Multivariable analysis revealed the presence of adenocarcinoma with any bronchioloalveolar features (P=.004) and being a never smoker (P=.006) were independent predictors of response.. Our data suggest that individuals in whom gefitinib is efficacious are more likely to have adenocarcinomas of the bronchioloalveolar subtype and to be never smokers. These observations may provide clues to mechanisms determining sensitivity to this agent and suggest that NSCLC has a different biology in patients who never smoked and those with bronchioloalveolar carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bronchoalveolar Lavage Fluid; Carcinoma, Bronchogenic; Carcinoma, Non-Small-Cell Lung; Epidermal Growth Factor; Female; Gefitinib; Humans; Logistic Models; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Protein-Tyrosine Kinases; Quinazolines; Retrospective Studies; Smoking

Gefitinib (Iressa, ZD 1839; AstraZeneca) is a selective Epidermal Growth Factor receptor tyrosine kinase inhibitor. In two randomized phase II trials (IDEAL 1 and IDEAL 2), it has demonstrated an activity against NSCLC, showing partial response and symptoms improvement rates respectively in about 20% and 40% of patients. Multivariate analyses revealed that being a woman, a non-smoker and having an adenocarcinoma was associated with response rate.. We describe a retrospective study of patients receiving Gefitinib as a third line compassionate treatment of NSCLC.. We enrolled 37 patients (29 men, 8 women). Tumors included 25 adenocarcinoma, 4 squamous cell carcinoma, 7 large cell carcinoma, and 1 neuroendocrine carcinoma. Partial response rate was 8.1%, and stable disease rate 27.0%. The 3 responders were all non-smoker women, with an histological type of adenocarcinoma. Symptoms improvement was observed in 59.5% of patients. Main toxicities were diarrhoea and skin reactions. We observed that responding patients had more adverse drugs-related reactions than stable or non-responding patients.. Gefitinib is a meaningful active therapy in NSCLC with a favorable toxicity profile. We suggest that being a woman, a never-smoker and having an adenocarcinoma may be clinical predictive factors of response to Gefitinib.

Topics: Adult; Aged; Antineoplastic Agents; Bronchial Neoplasms; Carcinoma, Bronchogenic; Carcinoma, Non-Small-Cell Lung; Epidermal Growth Factor; Female; Gefitinib; Humans; Male; Middle Aged; Palliative Care; Protein-Tyrosine Kinases; Quinazolines; Retrospective Studies; Sex Factors; Smoking

The objective of this study is to examine and characterize epidermal growth factor receptor (EGF-R) binding in inhaled plutonium-induced canine lung-tumor tissue and to compare it with that in normal canine lung tissue. Crude membrane preparations from normal and lung-tumor tissue from beagle dogs were examined in a radioreceptor assay, using 125I-labeled epidermal growth factor (EGF) as a ligand. Specific EGF receptor binding was determined in the presence of excess unlabeled EGF. We have examined EGF receptor binding in eight lung-tumor samples obtained from six dogs. Epidermal growth factor receptor binding was significantly greater in lung-tumor samples (31.38%) compared with that in normal lung tissue (3.76%). Scatchard plot analysis from the displacement assay revealed that there was no statistical difference in the binding affinity but significantly higher concentration of EGF-R sites in the lung-tumor tissue (619 fmol/mg) than in normal lung tissue (53 fmol/mg). The increase in EGF-R number in plutonium-induced dog lung tumors does not seem to correlate with increase in the initial lung burden exposure to plutonium. Our results demonstrate that there is a significant increase in EGF-R binding in inhaled plutonium-induced dog lung tumors.

Topics: Adenocarcinoma, Papillary; Administration, Inhalation; Animals; Binding, Competitive; Carcinoma, Bronchogenic; Dogs; Epidermal Growth Factor; ErbB Receptors; Female; In Vitro Techniques; Lung Neoplasms; Male; Membrane Proteins; Neoplasms, Radiation-Induced; Plutonium; Radioligand Assay

Three different human tumor lines in culture, a rhabdomyosarcoma, a bronchogenic carcinoma and a metastatic melanoma, release proteins (transforming growth factors, TGFs) into the medium that confer the transformed phenotype on untransformed fibroblasts. These proteins are acid and heat-stable; produce profound morphologic changes in rat and human fibroblasts; and enable normal anchorage-dependent cells to grow in agar. Removal of the transforming protein results in a reversion of cell phenotype. The major activity interacts with epidermal growth factor (EGF) cell membrane receptors. The peptides from these tumor cells are similar in their action to the sarcoma growth factor (SGF) released by murine sarcoma virus-transformed rodent cells. The most anchorage-independent tumor cells released the most TGFs. EGF-related TGFs were not detectable in fluids from cultures of cells with high numbers of free EGF membrane receptors (normal human fibroblasts and human carcinomas).

Topics: Adult; Aged; Animals; Binding, Competitive; Carcinoma, Bronchogenic; Carcinoma, Squamous Cell; Cell Division; Cell Transformation, Neoplastic; Cells, Cultured; DNA; Epidermal Growth Factor; ErbB Receptors; Female; Fibroblasts; Growth Substances; Humans; Lung Neoplasms; Male; Melanoma; Peptides; Rats; Receptors, Cell Surface; Rhabdomyosarcoma