A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC)†.

BACKGROUND: KRAS mutations are detected in 25% of non-small-cell lung cancer (NSCLC) and no targeted therapies are approved for this subset population. Trametinib, a selective allosteric inhibitor of MEK1/MEK2, demonstrated preclinical and clinical activity in KRAS-mutant NSCLC. We report a phase II trial comparing trametinib with docetaxel in patients with advanced KRAS-mutant NSCLC. PATIENTS AND METHODS: Eligible patients with histologically confirmed KRAS-mutant NSCLC previously treated with one prior platinum-based chemotherapy were randomly assigned in a ratio of 2 : 1 to trametinib (2 mg orally once daily) or docetaxel (75 mg/m(2) i.v. every 3 weeks). Crossover to the other arm after disease progression was allowed. Primary end point was progression-free survival (PFS). The study was prematurely terminated after the interim analysis of 92 PFS events, which showed the comparison of trametinib versus docetaxel for PFS crossed the futility boundary. RESULTS: One hundred and twenty-nine patients with KRAS-mutant NSCLC were randomized; of which, 86 patients received trametinib and 43 received docetaxel. Median PFS was 12 weeks in the trametinib arm and 11 weeks in the docetaxel arm (hazard ratio [HR] 1.14; 95% CI 0.75-1.75; P = 0.5197). Median overall survival, while the data are immature, was 8 months in the trametinib arm and was not reached in the docetaxel arm (HR 0.97; 95% CI 0.52-1.83; P = 0.934). There were 10 (12%) partial responses (PRs) in the trametinib arm and 5 (12%) PRs in the docetaxel arm (P = 1.0000). The most frequent adverse events (AEs) in ≥20% of trametinib patients were rash, diarrhea, nausea, vomiting, and fatigue. The most frequent grade 3 treatment-related AEs in the trametinib arm were hypertension, rash, diarrhea, and asthenia. CONCLUSION: Trametinib showed similar PFS and a response rate as docetaxel in patients with previously treated KRAS-mutant-positive NSCLC. CLINICALTRIALSGOV REGISTRATION NUMBER: NCT01362296.

Treatment of polymorphous light eruption with nicotinamide: a pilot study.

In a pilot study, 42 patients suffering from polymorphous light eruption (PLE) were treated with oral nicotinamide, 3 g daily, for 2 weeks. Twenty-five patients remained free from lesions despite extensive sun exposure. We suggest that an abnormality in tryptophan metabolism is important in the aetiology of PLE, and that nicotinamide administration partially corrects this.

Hepatitis A and B markers and presumable non-A, non-B hepatitis in a psychiatric institution.

The frequencies of hepatitis A and hepatitis B markers were determined in 291 members of the staff and 714 patients of a psychiatric institution for adults. 71.8% of the patients suffered from psychosis, 17.7% from neurosis, and 10.6% from oligophrenia. 84.4% of the patients and 69.2% of the staff were anti-HAV-positive. - 26.8% of the patients and 19.9% of the staff showed at least one HBV marker. The frequency of anti-HBc increased with age but not with hospitalization. Anti-HBc-positive persons did not show transaminase abnormalities more often as reported previously. - 2.6% of the patients were presumable Non-A, Non-B hepatitis cases after excluding IgM-anti-HAV, IgM-anti-CMV or -EBV and possible toxic effects. The rate of presumable Non-A, Non-B hepatitis equaled the frequency of HBsAg-positive persons.