Biological and clinical features in predicting efficacy of epidermal growth factor receptor tyrosine kinase inhibitors: a systematic review and meta-analysis.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), developed for patients with advanced non-small cell lung cancer (NSCLC), give modest results similar to those with chemotherapy. There is evidence of a greater survival benefit from TKIs in patients with certain molecular and clinical features, but results are conflicting. To assess the role of these factors in predicting TKI efficacy, a pooled analysis was performed on data from randomized trials in NSCLC. MATERIALS AND METHODS: An electronic search of all randomized trials comparing the efficacy or activity of TKIs and a pooled analysis were performed. The hazard ratio (HR) with 95% confidence interval (CI) was calculated for each level of the factors and an interaction test was used to detect differences in treatment effect related to the different levels. RESULTS: Of ten randomized trials identified, five were considered for analysis. Smoking was shown to be the only clinical factor to have a predictive effect (non smokers: overall survival (OS) HR 0.53, 95% CI 0.42-0.67; smokers: HR 0.91, 95% CI 0.81-1.02; p-value for interaction <0.001). A negative predictive value was suggested for K-ras mutations (K-ras(+): HR 1.97 95% CI 1.16-3.33; K-ras(-): HR 0.79, 95% CI 0.59-1.05; p-value for interaction 0.003). CONCLUSION: At the present time, none of the biological features which have been evaluated in patients who have undergone therapy using TKIs is proven to be of predictive value; only K-ras mutations and smoking habits can be considered as a possible criteria for selection. Results of prospective randomized trials on biological markers are awaited.

Osteonecrosis of the jaw (ONJ) in cancer patients treated with Bisphosphonates: how the knowledge of a phenomenon can change its evolution.

GOALS OF THE WORK: Osteonecrosis of the jaw (ONJ) is a severe complication of bisphosphonates treatment. Bisphosphonates reduce skeletal adverse events and give a clinical benefit to cancer patients. Therefore, it is necessary to identify appropriate procedures to reduce ONJ injures by using a successful monitoring program. In a retrospective study we analyzed the impact of a prevention program based on clinical oral cavity examination, dentists, and patients' education. The aim of the study was to evaluate if this approach might improve ONJ outcome in patients receiving pamidronate or zoledronate. MATERIALS AND METHODS: We analyzed retrospectively two different groups of patients treated at our Institution: patients treated from October 2003 to June 2005 (group A) and patients treated from June 2005 to April 2007 (group B). In June 2005 the prevention program started for all our patients. MAIN RESULTS: One hundred and eighty-six cancer patients with bone involvement, treated with bisphosphonates, were considered. Sixteen of them developed ONJ: eight before and eight after June 2005. We observed a consistent difference in the evolution of the two groups. In the first group, four patients underwent a major surgery (one partial maxillectomy, complicated by septic shock and oronasal communication; two partial mandibulectomies; and one segmental mandibular resection), with an important impairment of their quality of life; while the eight new ONJ cases, diagnosed after June 2005, were successfully treated without aggressive dental interventions, and achieved a good control of symptoms. CONCLUSIONS: Bisphosphonates-related ONJ is a frequent adverse event (8.6%). The monitoring program proved very efficient to improve the clinical outcome of ONJ, avoiding an aggressive treatment and using a conservative approach and medical therapy.