Assessment of erlotinib pharmacodynamics in tumors and skin of patients with head and neck cancer.

BACKGROUND: The purpose of the study was to evaluate the effects of erlotinib on epidermal growth factor receptor (EGFR)-related signaling elements in tumor and skin from patients with advanced squamous cell carcinoma of the head and neck (HNSCC) and seek relationships between relevant clinical, biological, and pharmacokinetic parameters. PATIENTS AND METHODS: Immunostaining for EGFR, p-EGFR, p-ERK, p-Akt, and p27 were analyzed semiquantitatively in serial tumor and skin samples from participating patients. Steady-state trough concentrations of erlotinib and its metabolite OSI-420 were also determined. RESULTS: Of 25 patients enrolled, 20 (80%) paired pre- and posttreatment skin biopsies and seven (28%) paired tumor biopsies were evaluable for at least one immunohistochemical parameter. The severity of skin toxicity related to time to progression (TTP) (P = 0.048) and overall survival (P < 0.001). C(ss,min) values for erlotinib and OSI-420 also related to TTP (P = 0.042 and 0.036, respectively). Erlotinib treatment was associated with decreased p-EGFR expression in 66% of evaluable tumor samples, which seemed related to increased TTP and survival, and p27 was up-regulated in 59% of evaluable skin biopsy samples following treatment. CONCLUSIONS: The feasibility of obtaining serial evaluable biopsies of HNSCC was suboptimal. Nevertheless, erlotinib inhibited p-EGFR in HNSCC tumors, which appeared associated to clinical benefit, and induced p27 in biopsies of normal skin.

Risk factors for colonization or infection due to methicillin-resistant Staphylococcus aureus in HIV-positive patients: a retrospective case-control study.

OBJECTIVE: To determine the risk factors for colonization or infection with methicillin-resistant Staphylococcus aureus in human immunodeficiency virus (HIV)-infected patients. DESIGN: Retrospective matched-pair case-control study. SETTING: Continuity clinic and inpatient HIV service of a university medical center. POPULATION: Patients with HIV infection from the general population of eastern and coastal Texas and from the Texas Department of Criminal Justice. DATA COLLECTION: Patient charts and the AIDS Care and Clinical Research Program Database were reviewed for the following: age, race, number of admissions, total hospital days, presence of a central venous catheter, serum albumin, total white blood cell count and absolute neutrophil count, invasive or surgical procedures, any cultures positive for S. aureus, and a history of opportunistic illnesses, diabetes, or dermatologic diagnoses. Data also were collected on the administration of antibiotics, antiretroviral therapy, steroids, cancer chemotherapy, and subcutaneous medications. RESULTS: In the univariate analysis, the presence of a central venous catheter, an underlying dermatologic disease, lower serum albumin, prior steroid therapy, and prior antibiotic therapy, particularly antistaphylococcal therapy or multiple courses of antibiotics, were associated with increased risk for colonization or infection with methicillin-resistant S. aureus. Multivariate analysis yielded a model that included presence of a central venous catheter, underlying dermatologic disease, broad-spectrum antibiotic exposure, and number of hospital days as independent risk factors for colonization or infection with methicillin-resistant S. aureus. CONCLUSIONS: In our HIV-infected patient population, prior hospitalization, exposure to broad-spectrum antibiotics, presence of a central venous catheter, and dermatologic disease were risk factors for acquisition of methicillin-resistant S. aureus.

Characteristics of the healthy worker effect: a comparison of male and female occupational cohorts.

The healthy worker effect (HWE) poses a serious methodological problem to investigators of occupational cohorts in that it may mask mortality excesses that result from occupational exposures. This problem is further complicated by the fact that the strength of the HWE generally varies according to sociodemographic, employment, and time-related factors. While the HWE has been well documented among numerous cohorts of male workers, little is known about its expression among female occupational workers. Follow-up mortality data on 44,154 employees from the Hanford nuclear facility for the period of 1944-1986 were examined using standardized mortality ratio (SMR) analysis to assess whether modifiers of the HWE were expressed differently in females than in males. Results of this analysis show that while the HWE was modified by race, age at hire, occupational class, and length of follow-up in both male and female cohorts, different patterns of modification emerged across the two subgroups. Learning about how gender differentiates expression of the HWE will help investigators more precisely assess the confounding effect of the HWE in studies of working cohorts. Therefore, this study's findings are relevant for designing and interpreting future occupational cohort studies.