Randomised, Phase II study of selumetinib, an oral inhibitor of MEK, in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer.

INTRODUCTION: Cisplatin and gemcitabine (CisGem) are standard chemotherapy for advanced biliary tract cancer (BTC). The MEK inhibitor selumetinib showed synergy with gemcitabine when administered sequentially in BTC. This randomised Phase 2 trial aimed to assess the efficacy of sequential or continuous selumetinib with CisGem. METHODS: Patients with advanced BTC received CisGem; arm A included selumetinib every day, arm B: selumetinib, days 1-5, 8-19 each cycle. Arm C received CisGem alone. Selumetinib was dosed at 75 mg BID but amended to 50 mg BID due to toxicity. RESULTS: In all, 51 participants were evaluable for response. No significant difference was seen in mean change in tumour size at 10 weeks between arms A and C (-7.8% vs -12.8%, P = 0.54) or arms B and C (-15% vs -12.8%, P = 0.78). There was no difference in median progression-free survival (6.0, 7.0, 6.3 months, P > 0.95) or overall survival (11.7, 11.7, 12.8 months, P = 0.70) for arms A, B and C, respectively. More participants experienced grade 3-4 toxicities in selumetinib-containing arms. More participants in arm A required chemotherapy dose reductions (P = 0.01) with lower chemotherapy dose intensity during the first 10 weeks. CONCLUSION: Adding sequential or continuous selumetinib to CisGem failed to improve efficacy and increased toxicity in patients with advanced BTC.

Legionnaires' Disease Cases at a Large Community Hospital-Common and Underdiagnosed.

Legionnaires' disease (LD) is a severe pneumonia with a mortality rate of about 10%. The illness remains largely underdiagnosed with outbreaks occurring with alarming incidence. In this study, we assessed the frequency of Legionnaires' disease among pneumonia cases treated at a large community hospital over a summer season. We invited all admitted patients diagnosed with pneumonia, able to provide a urine sample for an antigen test, presenting from May to October 2018, to enroll in our study; 35 patients were tested for the presence of Legionella. Out of 33 patients tested, 9 (28%) were positive for Legionella. Three sets of the 9 Legionella cases exhibited spatiotemporal clustering indicative of LD outbreaks. Only one of the 9 Legionella UAT-positive patients presented a sporadic case of LD. The number of pneumonia cases in our community confirmed to be LD was strikingly high (28%), compared to other survey studies that report between 3.7% and 14%. These results are consistent with previous knowledge that LD is underdiagnosed and support that routine testing should be considered for all possible LD cases, particularly in the summer months. Such testing is likely to prevent further cases of community acquired LD.