RESUMEN
Brain metastases occur in up to 25-55% of patients with metastatic HER2-positive breast cancer. Standard treatment has high rates of recurrence or progression, limiting survival and quality of life in most patients. Temozolomide (TMZ) is known to penetrate the blood-brain barrier and is US FDA approved for treatment of glioblastoma. Our group has demonstrated that low doses of TMZ administered in a prophylactic, metronomic fashion can significantly prevent development of brain metastases in murine models of breast cancer. Based on these findings, we initiated a secondary-prevention clinical trial with oral TMZ given to HER2-positive breast cancer patients with brain metastases after recent local treatment in combination with T-DM1 for systemic control of disease. Primary end point is freedom from new brain metastases at 1 year. (NCT03190967).
Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/prevención & control , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Telomerasa/metabolismo , Temozolomida/uso terapéutico , Animales , Antineoplásicos Alquilantes/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor , Neoplasias Encefálicas/terapia , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Proyectos de Investigación , Temozolomida/farmacologíaRESUMEN
This study tested the hypotheses that (1) parafunctional clenching increases pain and can lead to a diagnosis of temporomandibular disorder (TMD) pain and (2) electromyographic (EMG) activity during parafunctional clenching is significantly and positively correlated with reports of pain. Fourteen individuals without TMD participated in 5 consecutive days of 20-min long EMG biofeedback training sessions of the left and right temporalis and masseter muscles. Subjects were randomly assigned to either a Decrease or Increase group and were instructed to maintain EMG activity below 2 microV or above 10 microV during training, respectively. Two Increase subjects and no Decrease subjects were diagnosed, by a blinded examiner, with TMD pain following training. Self-reported pain posttraining was significantly higher for the Increase group. Masseter EMG activity was strongly correlated with pain. Parafunctional clenching increases pain and can lead to a diagnosis of TMD in otherwise pain-free individuals. Pain reports are positively correlated with the activity of the masseter muscle.