Role of Patient-Reported Outcomes in Clinical Trials in Metastatic Colorectal Cancer: A Scoping Review.

PURPOSE: To perform a scoping review on the use of Patient-Reported Outcome Measures (PROMs) in randomized trials on systemic therapy in patients with metastatic colorectal cancer (mCRC) between 2010 and 2021. METHODS: First, a search on clinicaltrials.gov was performed, looking for randomized trials in mCRC. The use of PROMs was analyzed quantitatively. Subsequently, we assessed the completeness of PROM reporting based on the CONSORT PRO extension in publications related to the selected trials acquired using Embase and PubMed. RESULTS: A total of 46/176 trials were registered on clinicaltrials.gov used PROMs. All these trials used validated PROM instruments. The EORTC QLQ-C30 was most frequently used (37 times), followed by the EQ-5D (21 times) and the EORTC QLQ-CR29 (six times). A total of 56/176 registered trials were published. In 35% (n = 20), the results of the PROMs were available. Overall, 7/20 (35%) trials documented all items of the CONSORT PRO extension and quality of reporting according to the CONSORT PRO extension was higher than in the period 2004-2012. In 3/20 (15%) of the published trials, the results of PROMs were not discussed nor included in the positioning of the new treatment compared to the reference treatment. CONCLUSION: When PROMs are used, the quality of reporting on patient-reported outcomes is improving, but this must continue in order to optimize the translation of trial results to individual patient values.

Pharmacy-based predictors of non-persistence with and non-adherence to statin treatment among patients on oral diabetes medication in the Netherlands.

AIMS: To evaluate statin non-persistence and non-adherence as discrete processes in diabetes patients, and identify pharmacy-based predictors of these processes in the first year after statin initiation. METHODS: We conducted a retrospective cohort study of statin initiators using a pharmacy database. Persistence and adherence were measured in the first, second and third year. Non-persistence was defined as a gap >180 days. Non-adherence was calculated in persistent patients and defined as a medication possession ratio <80%. Cox regression hazard ratios (HRs) and logistic regression odds ratios (ORs) were assessed for sociodemographic and medication-related factors as possible predictors. RESULTS: Of 12,741 initiators, 20.0% were non-persistent in the first year, while 9.0% and 7.5% were non-persistent in the second and third years. Non-adherence in persistent patients increased from 13.4% in the first to 15.6% and 18.1% in the second and third years. Predictors of non-persistence were female gender (HR: 1.10; 95% CI: 1.01-1.19), older age (HR: 1.52; 95% CI: 1.31-1.75), primary prevention (HR: 1.10; 95% CI: 1.00-1.20), initiating on low dose (HR: 1.44; 95% CI: 1.07-1.94) or standard dose (HR: 1.56; 95% CI: 1.16-2.10), and no cardiovascular co-medication (HR: 1.19; 95% CI: 1.07-1.33), while patients with four or more other medications were more likely to be persistent. Age <50 years (OR: 1.47; 95% CI: 1.22-1.77), low socioeconomic status (OR: 1.27; 95% CI: 1.12-1.45) and primary prevention (OR: 1.21; 95% CI: 1.07-1.38) were predictors of non-adherence, while females were more likely to be adherent (OR: 0.87; 95% CI: 0.77-0.98). CONCLUSION: Non-persistence was the foremost problem in the first year after statin initiation, while non-adherence in persistent patients increased in the second and third years. Pharmacy-based predictors of statin non-persistence were different from predictors of non-adherence among persistent patients.

Adjusting the DNA Interaction and Anticancer Activity of Pt(II) N-Heterocyclic Carbene Complexes by Steric Shielding of the Trans Leaving Group.

Five platinum(II) complexes bearing a (1,3-dibenzyl)imidazol-2-ylidene ligand but different leaving groups trans to it were examined for cytotoxicity, DNA and cell cycle interference, vascular disrupting properties, and nephrotoxicity. The cytotoxicity of complexes 3a-c increased with the steric shielding of their leaving chloride ligand, and complex 3c, featuring two triphenylphosphanes, was the most efficacious, with submicromolar IC50 concentrations. Complexes 3a-c interacted with DNA in electrophoretic mobility shift and ethidium bromide binding assays. The cationic complex 3c did not bind coordinatively to DNA but led to its aggregation, damage that is not amenable to the usual repair mechanisms. Accordingly, it arrested the cell cycle of melanoma cells in G1 phase, whereas cis-dichlorido[(1,3-dibenzyl)imidazol-2-ylidene](dimethyl sulfoxide) platinum(II) 3a induced G2/M phase arrest. Complex 3c also disrupted the blood vessels in the chorioallantoic membrane of fertilized chicken eggs. Ex vivo studies using precision-cut tissue slices suggested the nephrotoxicities of 3a-c to be clinically manageable.