Phase 0 study of vandetanib-eluting radiopaque embolics as a pre-operative embolization treatment in patients with resectable liver malignancies

PURPOSE: To assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemo-embolization in patients with resectable liver malignancies. METHODS: The VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years, had resectable hepatocellular carcinoma (HCC)(Child-Pugh A) or colorectal liver metastases (mCRC). Patients received 1mL of BTG-002814 transarterially (containing 100mg vandetanib) 7-21 days prior to surgery. Primary objectives were to establish the safety and tolerability of BTG-002814, and to determine concentrations of vandetanib and the N-desmethyl metabolite in plasma and resected liver post-treatment. Biomarker studies included circulating pro-angiogenic factors, perfusion computed tomography and dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI). RESULTS: Eight patients were enrolled: two with HCC, and six with mCRC. There was one Grade 3 adverse event (AE) pre-surgery and 18 post-surgery; six AEs were deemed BTG-002814 related. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days post-treatment with a mean maximum concentration (Cmax) of 24.3 ng/mL (SD 13.94) and present in resected liver tissue up to 32 days post-treatment (441-404,000 ng/g). Median tumor necrosis was 92.5% (range 5-100%). There were no significant changes in perfusion imaging parameters post-TACE. CONCLUSION: BTG-002814 has an acceptable safety profile in patients pre-surgery. Presence of vandetanib in tumor specimens up to 32 days post-treatment suggests sustained anticancer activity; low vandetanib plasma levels suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies

Prediction of Recovery, Dependence or Death in Elders Who Become Disabled During Hospitalization

BACKGROUND: Many older adults become dependent in one or more activities of daily living (ADLs: dressing, bathing, transferring, eating, toileting) when hospitalized, and their prognosis after discharge is unclear. OBJECTIVE: To develop a prognostic index to estimate one-year probabilities of recovery, dependence or death in older hospitalized patients who are discharged with incident ADL dependence. DESIGN: Retrospective cohort study. PARTICIPANTS: 449 adults aged ≥ 70 years hospitalized for acute illness and discharged with incident ADL dependence. MAIN MEASURES: Potential predictors included demographics (age, sex, race, education, marital status), functional measures (ADL dependencies, instrumental activities of daily living [IADL] dependencies, walking ability), chronic conditions (e.g., congestive heart failure, dementia, cancer), reason for admission (e.g., neurologic, cardiovascular), and laboratory values (creatinine, albumin, hematocrit). Multinomial logistic regression was used to develop a prognostic index for estimating the probabilities of recovery, disability or death over 1 year. Discrimination of the index was assessed for each outcome based on the c statistic. KEY RESULTS: During the year following hospitalization, 36 % of patients recovered, 27 % remained dependent and 37 % died. Key predictors of recovery, dependence or death were age, sex, number of IADL dependencies 2 weeks prior to admission, number of ADL dependencies at discharge, dementia, cancer, number of other chronic conditions, reason for admission, and creatinine levels. The final prognostic index had good to excellent discrimination for all three outcomes based on the c statistic (recovery: 0.81, dependence: 0.72, death: 0.78). CONCLUSIONS: This index accurately estimated the probabilities of recovery, dependence or death in adults aged 70 years or older who were discharged with incident disability following hospitalization. This tool may be useful in clinical settings to guide care discussions and inform decision-making related to post-hospitalization care