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.     

Parental Guidance and Children’s Healthy Food Consumption: Integrating the Theory of Planned Behavior with Interpersonal Communication Antecedents

The study of parenting practices on child food consumption has often been characterized as having great utility but lacking in theory. In contrast, the theory of planned behavior (TPB) has often been suggested to be limited in its utility. To address these gaps, interpersonal constructs – the concepts of active parental guidance (e.g., nutrition education) and restrictive parental guidance (e.g., rule-setting) – were integrated as antecedents to the original TPB variables in predicting child fruits and vegetables (FV) consumption. We surveyed 210 child/adolescent participants, aged between 10 and 16 in Singapore. Results from structural equation modeling showed that the integrative TPB model displayed an acceptable fit. Parental active guidance was associated with all three proximal predictors of behavior. Our results suggest that there are promising contributions to the theory of planned behavior in predicting child food consumption behavior by considering interpersonal antecedents.     

Retrieval of aspirated dental equipment from a lung

Canadian Journal of Anesthesia/Journal canadien d'anesthésie -