Phase I Dose-Escalation Study of SCB01A,a Microtubule Inhibitor with Vascular Disrupting Activity,in Patients with Advanced Solid Tumors

Lessons Learned

• SCB01A is a novel microtubule inhibitor with vascular disrupting activity.
• This first‐in‐human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity.
• SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.

BackgroundSCB01A, a novel microtubule inhibitor, has vascular disrupting activity.MethodsIn this phase I dose‐escalation and extension study, patients with advanced solid tumors were administered intravenous SCB01A infusions for 3 hours once every 21 days. Rapid titration and a 3 + 3 design escalated the dose from 2 mg/m² to the maximum tolerated dose (MTD) based on dose‐limiting toxicity (DLT). SCB01A‐induced cellular neurotoxicity was evaluated in dorsal root ganglion cells. The primary endpoint was MTD. Safety, pharmacokinetics (PK), and tumor response were secondary endpoints.ResultsTreatment‐related adverse events included anemia, nausea, vomiting, fatigue, fever, and peripheral sensorimotor neuropathy. DLTs included grade 4 elevated creatine phosphokinase (CPK) in the 4 mg/m² cohort; grade 3 gastric hemorrhage in the 6.5 mg/m² cohort; grade 2 thromboembolic event in the 24 mg/m² cohort; and grade 3 peripheral sensorimotor neuropathy, grade 3 elevated aspartate aminotransferase, and grade 3 hypertension in the 32 mg/m² cohort. The MTD was 24 mg/m², and average half‐life was ~2.5 hours. The area under the curve‐dose response relationship was linear. Nineteen subjects were stable after two cycles. The longest treatment lasted 24 cycles. SCB01A‐induced neurotoxicity was reversible in vitro.ConclusionThe MTD of SCB01A was 24 mg/m² every 21 days; it is safe and tolerable in patients with solid tumors.     

Polyvictimization and Psychiatric Sequelae Associated with Female Genital Mutilation/Cutting (FGM/C)

Female Genital mutilation/cutting (FGM/C) is associated with enduring psychiatric complications. In this study, we investigate the rates of co-morbid abuses and polyvictimization experienced by survivors of FGM/C. This is a sub-analysis of a cohort study examining the patient population at the EMPOWER Center for Survivors of Sex Trafficking and Sexual Violence in New York City. A retrospective chart-review of electronic medical records was conducted for all consenting adult patients who had FGM/C and had an intake visit between January 16, 2014 and March 6, 2020. Of the 80 participants, ages ranged from 20 to 62 years with a mean of 37.4 (SD?=?9.1) years. In addition to FGM/C, participants were victims of physical abuse (43; 53.8%), emotional abuse (35; 43.8%), sexual abuse (35; 43.8%), forced marriage (20; 25%), child marriage (13; 16.3%), and sex trafficking (1; 1.4%). There was a high degree of polyvictimization, with 41 (51.2%) experiencing 3 or more of the aforementioned abuses. Having FGM/C on or after age 13 or having a higher total abuse score was also found to be strong predictors of depression and PTSD. The high rates of polyvictimization among survivors of FGM/C are associated with development of depression and PTSD. Despite co-morbid abuses, patients still attribute substantial psychiatric symptoms to their FGM/C. Health care providers should understand the high risk of polyvictimization when caring for this patient population.

     

Americans' Awareness, Knowledge, and Behaviors Regarding Fats: 2006-2007

In recent years, epidemiologic and clinical studies, public and regulatory policy activity, and media coverage have focused on issues related to trans fats. To help increase awareness and understanding of trans fats and other fats, the American Heart Association (AHA) launched the “Face the Fats” national consumer education campaign in April 2007. The AHA commissioned a quantitative tracking survey between 2006 and 2007 to measure changes in consumer awareness, knowledge, and behaviors related fats and oils and their perceived impact on heart disease. The survey was conducted by Cogent Research. Data were collected during March 2006 and May 2007. At both time points, the survey included a representative sample of the American population age 18 to 65 years (n=1,000). The sampling plan for the survey was designed based on the 2000 and 2003 US Census. The margin of error was ±3.10 percentage points. Awareness of trans fats increased during the 1-year study period. In 2007, 92% of respondents were aware of trans fats, an increase from 84% in 2006 (P<0.05). The 2007 level was similar to the awareness of saturated fats (93%). Perceptions that certain fats and oils heighten the risk of heart disease increased for trans fats (73% in 2007 vs 63% in 2006; P<0.05), saturated fats (77% in 2007 vs 73% in 2006; P<0.05), and partially hydrogenated oils (56% in 2007 vs 49% in 2006; P<0.05). Knowledge about food sources of different fats remained low. On an unaided basis, 21% could name three food sources of trans fats in 2007, up from 17% in 2006 (P<0.05). Knowledge of food sources of saturated fat remained unchanged at 30% in 2007. Significantly more respondents in 2007 reported behavioral changes related to trans fat information, such as buying food products because they show “zero trans fat” on labels or packages (37% in 2007 vs. 32% in 2006; P<0.05). Between 2006 and 2007, consumer awareness about trans fats increased and attained awareness levels similar to saturated fats. The increased awareness is associated with improved self-reported behaviors in grocery shopping. Nonetheless, overall knowledge, especially regarding food sources of saturated and trans fats, remains relatively low, underscoring the need for heightened consumer education activities. The positive change in consumer awareness about trans fats is likely attributable to the wide range of messages available to them, including the AHA “Face the Fats” national consumer education campaign.     

Intrapersonal, Interpersonal, and Contextual Factors in Engaging in and Responding to Extramarital Involvement

Extramarital involvement (EMI) occurs with high prevalence among couples in clinical and community settings, frequently resulting in considerable distress both to participants and their spouses. The field lacks a synthesized review of this literature. Without such a synthesis, it has been difficult for researchers and clinicians to have an understanding of what is and is not known about EMI. This article reviews the large and scattered EMI literature using a framework that encompasses multiple source domains across the temporal process of engaging in and responding to EMI. In addition, this review delineates conceptual and methodological limitations to previous work in this area and articulates directions for further research.     

Depressive Symptoms Among HIV Positive Men: Life Stress,Coping, and Social Support1

The significance of life stress, coping, and social support was examined in relation to depressive symptomatology in a sample of 160 asymptomatic and mildly symptomatic HIV-antibody-positive (HIV+) men. The participants (mean age = 32 years) were interviewed about the life stress that they had experienced in the previous 6