Prognostic and predictive value of epidermal growth factor receptor tyrosine kinase domain mutation status and gene copy number for adjuvant chemotherapy in non-small cell lung cancer.

PURPOSE: Patients with non-small cell lung carcinoma with epidermal growth factor receptor (EGFR) mutations may have a more favorable prognosis and greater response to chemotherapy. The effect of EGFR mutation and gene copy on patients with early-stage non-small cell lung carcinoma receiving adjuvant chemotherapy has not been reported. PATIENTS AND METHODS: Tumor samples from NCIC Clinical Trials Group JBR.10, an adjuvant trial of vinorelbine/cisplatin adjuvant chemotherapy [ACT] versus observation (OBS), were analyzed for EGFR mutation by multiple sensitive methods and copy number by fluorescent in situ hybridization. Their prognostic and predictive roles were explored in correlation with survival. RESULTS: Mutation results were available in 221 OBS and 215 ACT and fluorescent in situ hybridization results in 159 OBS and 163 ACT patients. Mutations were identified in 43 (27 OBS and 16 ACT) patients (36 sensitizing exon 19 deletions or L858R mutations). Compared with wild-type, sensitizing mutations were not significantly prognostic in OBS patients (hazard ratio [HR]: 0.79, 95% confidence interval [CI]: 0.38-1.63, p = 0.53). Although the presence of sensitizing mutations resulted in relatively greater benefit in ACT patients (HR: 0.44, 95% CI: 0.11-1.70, p = 0.22) compared with wild-type patients (HR: 0.78, 95% CI: 0.58-1.06, p = 0.12), this quantitative difference was not significant (interaction p = 0.50). Similarly, high EGFR copy was neither significantly prognostic nor predictive, although quantitatively it was associated with greater benefit from ACT. CONCLUSIONS: Trends toward longer survival and a greater benefit from chemotherapy were observed in patients with exon 19/21 mutations and high EGFR copy, although the differences were not statistically significant. The interpretation of the results was limited by the low EGFR mutation rate in this study of mainly white patients.

Lung cancer in a U.S. population with low to moderate arsenic exposure.

BACKGROUND: Little is known about the carcinogenic potential of arsenic in areas with low to moderate concentrations of arsenic (< 100 microg/L) in drinking water. OBJECTIVES: We examined associations between arsenic and lung cancer. METHODS: A population-based case-control study of primary incident lung cancer was conducted in 10 counties in two U.S. states, New Hampshire and Vermont. The study included 223 lung cancer cases and 238 controls, each of whom provided toenail clippings for arsenic exposure measurement by inductively coupled-plasma mass spectrometry. We estimated odds ratios (ORs) of the association between arsenic exposure and lung cancer using unconditional logistic regression with adjustment for potential confounders (age, sex, race/ethnicity, smoking pack-years, education, body mass index, fish servings per week, and toenail selenium level). RESULTS: Arsenic exposure was associated with small-cell and squamous-cell carcinoma of the lung [OR = 2.75; 95% confidence interval (CI), 1.00-7.57] for toenail arsenic concentration > or = 0.114 microg/g, versus < 0.05 microg/g. A history of lung disease (bronchitis, chronic obstructive pulmonary disease, or fibrosis) was positively associated with lung cancer (OR = 2.86; 95% CI, 1.39-5.91). We also observed an elevated risk of lung cancer among participants with a history of lung disease and toenail arsenic > or = 0.05 microg/g (OR = 4.78; 95% CI, 1.87-12.2) than among individuals with low toenail arsenic and no history of lung disease. CONCLUSION: Although this study supports the possibility of an increased risk of specific lung cancer histologic types at lower levels of arsenic exposure, we recommend large-scale population-based studies.

Docetaxel in the treatment of esophageal cancer.

Esophageal cancer is the ninth most common malignancy in the world and the seventh leading cause of death in American men. Because symptoms are often intermittent and vague, patients typically present at an advanced stage, with limited survival. In operable patients, standard care includes surgery with or without adjuvant chemotherapy and radiotherapy; chemotherapy and radiotherapy is the standard care for inoperable disease. Docetaxel, a taxane that promotes polymerization of tubules and inhibits depolymerization of microtubules, has shown in vitro and in vivo antitumor effects on human gastric cell lines and gastric cancer xenografts. These antitumor effects have led to the evaluation of docetaxel as a single agent and in combination with other agents and modalities in patients with esophageal cancer. Results of relevant trials are reviewed herein.