Treating persistent depressive symptoms in post-ACS patients: The project COPES phase-I randomized controlled trial

Depression and sub-syndromal depressive symptoms are important predictors of morbidity and mortality after acute coronary syndrome (ACS). Prior trials of depression treatment in post-ACS patients have demonstrated no improvement for event-free survival, and only modest improvement in depression symptoms. These trials have raised a number of important issues regarding timing of depression intervention, acceptability of depression treatment to ACS patients, and safety for subsets of the treated population. This article describes Project COPES (Coronary Psychosocial Evaluation Studies), a multi-center Phase-I randomized clinical trial. Project COPES uses a patient preference depression treatment that has previously been found acceptable to medical patients, and a 3-month pre-randomization observation period to insure depression status. The study sample will include 200 post-ACS patients. The primary outcome is patient satisfaction with depression care. Secondary, exploratory aims include the acceptability of depression treatment, reduction in depressive symptoms, and the effects of treatment on two key pathways – medication adherence and inflammation – hypothesized to link depression to post-ACS prognosis. These analyses will provide important data to inform subsequent clinical trials with this population

Advanced Phase I/II Studies of Targeted Gene Delivery In Vivo: Intravenous Rexin-G for Gemcitabine-resistant Metastatic Pancreatic Cancer

Rexin-G, a nonreplicative pathology-targeted retroviral vector bearing a cytocidal cyclin G1 construct, was tested in a phase I/II study for gemcitabine-resistant pancreatic cancer. The patients received escalating doses of Rexin-G intravenously from 1 × 1011 colony-forming units (cfu) 2–3× a week (dose 0–1) to 2 × 1011 cfu 3× a week (dose 2) for 4 weeks. Treatment was continued if there was less than or equal to grade 1 toxicity. No dose-limiting toxicity (DLT) was observed, and no vector DNA integration, replication-competent retrovirus (RCR), or vector-neutralizing antibodies were noted. In nine evaluable patients, 3/3 patients had stable disease (SD) at dose 0–1. At dose 2, 1/6 patients had a partial response (PR) and 5/6 patients had SD. Median progression-free survival (PFS) was 3 months at dose 0–1, and >7.65 months at dose 2. Median overall survival (OS) was 4.3 months at dose 0–1, and 9.2 months at dose 2. One-year survival was 0% at dose 0–1 compared to 28.6% at dose 2, suggesting a dose–response relationship between OS and Rexin-G dosage. Taken together, these data indicate that (i) Rexin-G is safe and well tolerated, and (ii) Rexin-G may help control tumor growth, and may possibly prolong survival in gemcitabine-resistant pancreatic cancer, thus, earning US Food and Drug Administration's (FDA) fast-track designation as second-line treatment for pancreatic cancer