PREMIUM: A French prospective multicenter observational study of factors impacting on efficacy and compliance to cetuximab treatment in first-line KRAS wild-type metastatic colorectal cancer.

BACKGROUND: Cetuximab improves progression-free survival (PFS) and overall survival (OS) in patients with KRAS wild type (wt) metastatic colorectal cancer (mCRC). Few data are available on factors impacting both efficacy and compliance to cetuximab treatment, which is, in combination with chemotherapy, a standard-of-care first-line treatment regimen for patients with KRAS wt mCRC. PATIENTS AND METHODS: PREMIUM is a prospective, French multicenter, observational study that recruited patients with KRAS wt mCRC scheduled to receive cetuximab, with or without first-line chemotherapy, as part of routine clinical practice, between October 28, 2009 and April 5, 2012 (ClinicalTrials.gov Identifier: NCT01756625). The main endpoints were the factors impacting on efficacy and compliance to cetuximab treatment. Predefined efficacy endpoints were PFS and safety. RESULTS: A total of 493 patients were recruited by 94 physicians. Median follow-up was 12.9 months. Median progression-free survival was 11 months [9.6-12]. In univariate analyses, ECOG performance status (PS), smoking status, primary tumor location, number of metastatic organs, metastasis resectability, surgery, folliculitis, xerosis and paronychia maximum grade, and acne preventive treatment were statistically significant. In multivariate analysis (Hazard Ratios of multivariate stepwise Cox models), ECOG PS, surgery, xerosis and folliculitis were positive prognostics factors for longer PFS. Among all patients, 69 (14%) were non-compliant. In multivariate analysis, no variables were statistically significant. The safety profile of cetuximab was consistent with previous studies. CONCLUSIONS: ECOG PS <2, surgical treatment performed, and maximum grade xerosis or folliculitis developed were predictive factors of cetuximab efficacy on KRAS wt mCRC patients. Unfortunately, we failed in identifying predictive factors for compliance in these patients.

Ultrasound processing of liquid system(s) and its antimicrobial mechanism of action.

Ultrasound creates cavitation phenomena, resulting in the formation of several free radicals, namely OH˙ and H˙, due to the breakdown of the H2 O molecule. These radicals affect the cellular integrity of the bacteria, causing the inactivation of several processes, and thus it is important to unravel the mechanism of action of this technology. This research looks into the application and mechanism of action of ultrasound technology as a means of disinfection by acoustic cavitation. Sterile water and synthetic waste water were inoculated with different mutants of Escherichia coli K12 strains containing deletions in genes affecting specific functional properties of E. coli. These were: dnak soxR, soxS, oxyR, rpoS, gadA/gadB, gadC and yneL. Escherichia coli K-12 ΔoxyR appeared to be more resistant to the treatment together with gadW, gadX, gabT and gabD, whereas the mutant K-12 ΔdnaK was more sensitive with c. 2·5 log (CFU per ml) reduction in comparison to their isogenic wild-type E. coli K-12. This indicates that the dnaK gene participates in general stress response and more specifically to hyperosmotic stress. The other E. coli deleted genes tested (soxS, rpoS, gadB, gadC, yneL) did not appear to be involved in protection of microbial cells against ultrasound. SIGNIFICANCE AND IMPACT OF THE STUDY: This study looks at the mechanism of action of ultrasound technology for the disinfection of wastewater. Different mutants with deleted genes were used to study the respective sensitivity or resistance to this treatment. This is essential to characterize changes at the molecular level, which might be occurring during treatment, resulting in bacterial adaptation.