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1.
Neurosurgery ; 79(2): E305-12, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27309344

RESUMEN

BACKGROUND AND IMPORTANCE: A porous bioresorbable polymer scaffold has previously been tested in preclinical animal models of spinal cord contusion injury to promote appositional healing, spare white matter, decrease posttraumatic cysts, and normalize intraparenchymal tissue pressure. This is the first report of its human implantation in a spinal cord injury patient during a pilot study testing the safety and feasibility of this technique (ClinicalTrials.gov Identifier: NCT02138110). CLINICAL PRESENTATION: A 25-year-old man had a T11-12 fracture dislocation sustained in a motocross accident that resulted in a T11 American Spinal Injury Association Impairment Scale (AIS) grade A traumatic spinal cord injury. He was treated with acute surgical decompression and spinal fixation with fusion, and enrolled in the spinal scaffold study. A 2 × 10 mm bioresorbable scaffold was placed in the spinal cord parenchyma at T12. The scaffold was implanted directly into the traumatic cavity within the spinal cord through a dorsal root entry zone myelotomy at the caudal extent of the contused area. By 3 months, his neurological examination improved to an L1 AIS grade C incomplete injury. At 6-month postoperative follow-up, there were no procedural complications or apparent safety issues related to the scaffold implantation. CONCLUSION: Although longer-term follow-up and investigation are required, this case demonstrates that a polymer scaffold can be safely implanted into an acutely contused spinal cord. This is the first human surgical implantation, and future outcomes of other patients in this clinical trial will better elucidate the safety and possible efficacy profile of the scaffold. ABBREVIATIONS: AIS, American Spinal Injury Association Impairment ScaleSCI, spinal cord injurytSCI, traumatic spinal cord injury.


Asunto(s)
Implantes Absorbibles , Traumatismos de la Médula Espinal/cirugía , Fracturas de la Columna Vertebral/cirugía , Vértebras Torácicas/lesiones , Andamios del Tejido , Adulto , Descompresión Quirúrgica , Estudios de Factibilidad , Humanos , Masculino , Examen Neurológico , Proyectos Piloto , Polímeros , Resultado del Tratamiento
2.
Cancer Chemother Pharmacol ; 77(5): 997-1003, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-27025608

RESUMEN

PURPOSE: VS-6063 (also known as defactinib or PF-04554878) is a second-generation inhibitor of focal adhesion kinase and proline-rich tyrosine kinase-2. This phase 1 study evaluated the safety and tolerability, pharmacokinetics, and clinical activity of VS-6063 in Japanese subjects with advanced solid tumor malignancies in a first-in-Asian study setting. METHODS: VS-6063 was administered orally twice daily (b.i.d.) in 21-day cycles to cohorts of three subjects each with a standard 3 + 3 dose-escalation design until disease progression or unacceptable toxicity. Blood samples for pharmacokinetics were collected on Day 1 and 15. The assessments were performed using CTCAE v4.0 for adverse events (AEs), and the Response Evaluation Criteria In Solid Tumors, version v1.1 (RECIST v1.1) for tumor response. RESULTS: Nine patients were treated across three dose levels (200-600 mg BID). No dose-limiting toxicities were observed at any dose level. Most frequent treatment-related AEs were Grade 1/2 unconjugated hyperbilirubinemia, fatigue, decreased appetite, and diarrhea. Only one subject in the 200 mg BID cohort experienced reversible and transient Grade 3 unconjugated hyperbilirubinemia. PK analyses confirmed that the exposure at the recommended Phase 2 dose (RP2D) of 400 mg BID was comparable with exposures previously reported in non-Japanese subjects. Durable stable disease of approximately 24 weeks was confirmed in two subjects (malignant mesothelioma and rectal cancer). CONCLUSIONS: VS-6063 was well tolerated at all dose levels investigated in this first-in-Asian study. These data support the administration of VS-6063 to Japanese subjects at the RP2D in clinical trials involving solid tumor malignancies.


Asunto(s)
Antineoplásicos/administración & dosificación , Benzamidas/administración & dosificación , Quinasa 1 de Adhesión Focal/antagonistas & inhibidores , Quinasa 2 de Adhesión Focal/antagonistas & inhibidores , Neoplasias/tratamiento farmacológico , Pirazinas/administración & dosificación , Sulfonamidas/administración & dosificación , Administración Oral , Adulto , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Área Bajo la Curva , Pueblo Asiatico , Benzamidas/efectos adversos , Benzamidas/farmacocinética , Benzamidas/uso terapéutico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Semivida , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/enzimología , Neoplasias/orina , Pirazinas/efectos adversos , Pirazinas/farmacocinética , Pirazinas/uso terapéutico , Criterios de Evaluación de Respuesta en Tumores Sólidos , Sulfonamidas/efectos adversos , Sulfonamidas/farmacocinética , Sulfonamidas/uso terapéutico
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