Sorafenib with or without everolimus in patients with advanced hepatocellular carcinoma (HCC): a randomized multicenter, multinational phase II trial (SAKK 77/08 and SASL 29).

BACKGROUND: Sorafenib (S), a multitargeted tyrosine kinase inhibitor, is the standard of care for first-line systemic treatment of advanced hepatocellular carcinoma (HCC). Everolimus (E) is a potent inhibitor of mTOR, a pathway frequently activated in HCC. Preclinical data suggest that the combination S + E has additive effects compared with single-agent S. PATIENTS AND METHODS: Patients with unresectable or metastatic HCC and Child-Pugh ≤7 liver dysfunction were randomized to receive daily S 800 mg alone or with E 5 mg until progression or unacceptable toxicity. The primary end point was progression-free survival at 12 weeks (PFS12). The secondary end points included response rate, PFS, time to progression (TTP), overall survival (OS), duration of disease stabilization (DDS), safety, and quality-of-life (QoL) assessments. RESULTS: A total of 106 patients were randomized: 46 patients received S and 60 patients received S + E. Ninety-three patients were assessable for the primary end point and 105 patients for the safety analysis. The PFS12 rate was 70% [95% confidence interval (CI) 54-83] and 68% (95% CI 53-81) in patients randomized to S and S + E, respectively. The RECIST (mRECIST) response rate was 0% (23%) in the S arm and 10% (35%) in the S + E arm. Median PFS (6.6 versus 5.7 months), TTP (7.6 versus 6.3 months), DDS (6.7 versus 6.7 months), and OS (10 versus 12 months) were similar in the S and S + E arms, respectively. Grade 3/4 adverse events occurred in 72% and 86% of patients in arm S and arm S + E, respectively. Patients had similar QoL scores over time, except for a greater worsening in physical well-being and mood in the arm S + E. CONCLUSIONS: No evidence was found that S + E improves the efficacy compared with S alone. Combining 5 mg E with full-dose S is feasible, but more toxic than S alone. Further testing of this drug combination in molecularly unselected HCCs appears unwarranted. CLINICALTRIALSGOV: NCT01005199.

Routine disinfection of patients' environmental surfaces. Myth or reality?

We have evaluated the need for daily disinfection of environmental surfaces not contaminated by biological fluids, in patient areas of a medical unit with two wings [North (N) and South (S)] at the University Hospitals of Geneva, Switzerland. Weekly bacteriological monitoring of surfaces was carried out at random (N = 1356 samples). In the S wing (control), we used detergent/disinfectant for daily cleaning of the floors and furniture. In the N wing we began by using a detergent for floors and furniture; after four weeks the results suggested changing to a rotation of detergent, dust attracting disposable dry mops and disinfectant. During this period the furniture was cleaned with an active oxygen-based compound. The average differences in contamination before and after cleaning floors were (mean reduction in bacterial counts and 95% confidence intervals; CI95): disposable mops: 92.7 cfu/24 cm2 (CI95; 74-112), active oxygen based compound 111.1 (90-133), and quaternary ammonium compound -0.6 (-27-26). Use of detergent alone was associated with a significant increase in bacterial colony counts: on average by 103.6 cfu (CI95 73-134). The quaternary ammonium compound was inadequate for disinfecting bathrooms and toilets but the active oxygen based compound was satisfactory. For furniture, there was a significant reduction in bacterial counts with both the methods using disinfectants. As the detergent was contaminated, by using it alone for cleaning, we were actually seeding surfaces with bacteria. A total of 1117 patients was studied and we observed no change in the incidence of nosocomial infections during the four months of the trial. In conclusion, uncontrolled routine disinfection of environmental surfaces does not necessarily make it safe for the patient and could seed the environment with potential pathogens.