BACKGROUND:The Lapatinib Expanded Access Program (LEAP) was designed to provide access to lapatinib plus capecitabine for HER2-positive metastatic breast cancer patients who previously received an anthracycline, a taxane, and a trastuzumab and had no other treatment options.PATIENTS AND METHODS:LEAP opened globally and enrollment continued until lapatinib received regulatory approval in each participating country. Patients were assessed for progression-free survival (PFS) and overall survival (OS) and monitored for serious adverse events (SAEs).RESULTS:As of 30 September 2008, 4283 patients from 45 countries enrolled in LEAP. The median treatment duration was 24.7 weeks. The most common drug-related SAEs were diarrhea (9.7%), vomiting (4.3%), and nausea (2.4%) and were mainly grade 3 or higher. The incidences of special interest SAEs were decreased left ventricle ejection fraction (0.5%), interstitial lung disease/pneumonitis (0.2%), and serious hepatobiliary events (0.4%). This safety profile is consistent with the overall lapatinib program. The median PFS and OS were 21.1 [95% confidence interval (CI) = 20.1-22.3] and 39.6 (95% CI = 37.7-40.7) weeks, respectively (n = 4006). Subgroup analysis showed longer PFS and OS in patients who had not received prior capecitabine.CONCLUSIONS:These results demonstrate the safety and efficacy of lapatinib in a broader patient population compared with a clinical trial.

The present article provides a narrative review of empirical studies on metacognitive training in psychosis (MCT). MCT represents an amalgam of cognitive-behavioral therapy (CBT), cognitive remediation (CRT) and psychoeducation. The intervention is available in either a group (MCT) or an individualized (MCT +) format. By sowing the seeds of doubt in a playful and entertaining fashion, the program targets positive symptoms, particularly delusions. It aims to raise patients’ awareness for common cognitive traps or biases (e.g., jumping to conclusions, overconfidence in errors, bias against disconfirmatory evidence) that are implicated in the formation and maintenance of psychosis. The majority of studies confirm that MCT meets its core aim, the reduction of delusions. Problems (e.g., potential allegiance effects) and knowledge gaps (i.e., outcome predictors) are highlighted. The preliminary data suggest that the individual MCT format is especially effective in addressing symptoms, cognitive biases and insight. We conclude that MCT appears to be a worthwhile complement to pharmacotherapy.

The authors performed a critical study of the macro-volumetric method for the determination of anthranilic acid by di- and tri-brommation. Preference was given to the tribromination method, as it was found to be more precise.