Search

Purpose: Drug development in oncology is resource intensive and has a high failure rate. In this exploratory analysis, we aimed to identify the characteristics and outcomes of published Phase I studies associated with future Food and Drug Administration (FDA) approval., Methods: Phase I studies of approved and non-approved anticancer agents between 2000 and 2013 were retrospectively examined. Fisher's exact and chi-squared tests were used to compare the potential predictive measures., Results: Phase I studies of 88 anticancer agents (54 approved and 34 non-approved by the FDA), treating a total of 4,423 subjects, were examined. The median number of patients in Phase I trials of approved and non-approved agents was 44.5 and 32, respectively. A total of 423 subjects (86 reporting studies) had a complete responses, and 342 subjects (80 reporting studies) had a partial responses (PR). A higher number of PR (P < 0.001), PR rate (P = 0.003) and longer PR duration (P = 0.001) were predictive of regulatory success., Conclusions: These preliminary findings indicate that objective responses in Phase I trials may have predictive value for later regulatory approval.

Background/introduction: The purpose of this study was to describe the basic demographic characteristics, and analyze the response and survival experience of advanced renal cancer subjects treated in a phase I trial., Patients and Methods: We conducted a retrospective observational study in 70 renal cancer patients participating in 25 phase I trials. Descriptive statistics, Kaplan-Meier, and multivariate Cox proportional hazards analyses were used to examine factors associated with time from study entry to treatment failure (TTF) and survival., Results: The median age at diagnosis was 56.50 years. Eastern Cooperative Oncology Group (ECOG) performance status was 0 for 23.19% (n = 16) of the patients; 49.18% (n = 30) had received 2 or more previous lines of systemic therapy; and 84.29% (n = 59) of patients had 2 or more metastatic sites. A median number of 4.00 cycles of treatment was delivered. Four partial responses (6.25%) and 38 cases of stable disease lasting > 4 months (43.75%) were observed. The median TTF was 16.00 weeks. In multivariate analyses, men and patients with lactate dehydrogenase > 1.5 times the upper limit of normal had a shorter TTF. The median overall survival was 45.57 weeks (319.00 days). In multivariate analysis, factors predicting shorter survival were ECOG performance status ≥ 1 (P = .023), age younger than 60 years (P = .015), albumin < 3.4 g/dL (P = .042), and liver metastases (P = .010)., Conclusion: Advanced renal cancer patients with select clinical characteristics could consider phase I trials after exhausting standard therapeutic options., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: We sought to perform the first characterization of vasopressin and other vasoactive mediators released during resuscitation of hypotensive trauma patients., Methods: This institutional review board-approved study was conducted under waiver of consent. Adults with clinical evidence of acute traumatic injury and systolic blood pressure less than or equal to 90 mm Hg within 1 hour of arrival were evaluated at our Level I trauma center. Two hundred three patients were screened with 50 enrolled from February 2010 to February 2011. Demographic information was also collected. Blood samples were obtained at 0, 30, 60, 90, 120, and 240 minutes after arrival, and assays were performed for vasopressin, angiotensin II, epinephrine, and cortisol. We assessed the significance of variation in these vasoactive mediators with injury and transfusion of more than 600 mL, with adjustment for time using repeated-measures linear models in log units., Results: We found that vasopressin (p = 0.005) and epinephrine (p = 0.01) increased significantly with injury, while angiotensin (p = 0.60) and cortisol (p = 0.46) did not and that vasopressin (p < 0.001) and epinephrine (p = 0.004) increased significantly in patients requiring transfusion of more than 600 mL but angiotensin II (p = 0.11) and cortisol (p = 0.90) did not. Relatively low levels of vasopressin (<30 pg/mL) were observed at least once during the first 2 hours in 88% of trauma patients, and abnormally low epinephrine levels (<100 pg/mL) were observed at least once during the first 2 hours in 18% of trauma patients., Conclusion: This is the first clinical trial to serially evaluate vasopressin and other vasoactive mediators following trauma during the resuscitation phase. Vasopressin, in particular, and epinephrine seem to be the key mediators produced in the human response to severe injury. A deficiency of vasopressin may contribute to intractable shock after trauma., Level of Evidence: Prognostic/epidemiologic study, level III.

An 11-point (0-10) scale for measuring the degree of lethality of suicide attempts is presented. The scale has nine example "anchors" and uses the relative lethality of an extensive table of drugs. The psychometric studies show the scale to be of at least equal-interval, possibly even ratio measurement level. The equal-interval quality allows suicidal behaviors to be specified in numeric relationship to each other relieving us of the burden of using unquantified labels such as "mild," "moderate," and "serious." Having a standardized, commonly used reference scale should greatly facilitate our research and clinical efforts to communicate our findings. The scale can be used reliably by nonmedical personnel with no prior training.