RESUMO
Fifteen patients with treatment-refractory colorectal cancer were enrolled on a phase 1b study of Pexa-Vec (pexastimogene devacirepvec; JX-594), an oncolytic and immunotherapeutic vaccinia designed to selectively replicate in cancer cells. Pexa-Vec was administered intravenously every 14 days, at dose levels of 1 × 10(6), 1 × 10(7), or 3 × 10(7) plaque-forming units (pfu)/kg. The primary endpoint was to determine the maximum tolerated dose. Secondary endpoints were pharmacokinetics and pharmacodynamics as well as antitumor activity. Patients were heavily pretreated (mean 4.5 lines of therapy). All patients received at least two Pexa-Vec doses (median = 4; range = 2-4). No dose-limiting toxicities were reported, and the maximum tolerated dose was not reached. The most common adverse events were grade 1/2 flu-like symptoms, generally lasting <24 hours. During the first and last cycles, genome pharmacokinetics were unchanged. Infectious pfu could be detected in plasma up to 2 hours after cycle 1 and up to 30 minutes after cycle 4 (when antivaccinia antibody titers are known to have peaked). Ten patients (67%) had radiographically stable disease. Given the acceptable safety profile of multiple intravenous Pexa-Vec infusions in patients with treatment-refractory colorectal cancer, further trials evaluating efficacy of intravenous Pexa-Vec, as monotherapy or in combination with chemotherapeutic agents, is warranted in this patient population.
Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/terapia , Vetores Genéticos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Imunoterapia , Terapia Viral Oncolítica , Vírus Oncolíticos/genética , Vaccinia virus/genética , Administração Intravenosa , Adulto , Idoso , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Terapia Combinada , Citocinas/sangue , Esquema de Medicação , Feminino , Vetores Genéticos/administração & dosagem , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Terapia Viral Oncolítica/efeitos adversos , Terapia Viral Oncolítica/métodos , Dermatopatias/etiologia , Dermatopatias/patologia , Resultado do TratamentoRESUMO
PURPOSE: This study was done to identify effects of carbonated water intake on constipation in elders who have experienced a cerebrovascular accident (CVA) and are bed-ridden. METHODS: Forty elderly patients with CVA were randomly assigned to one of two groups in a double-blind study. Patients in the experimental group drank carbonated water and those in the control group drank tap water for two weeks. Six patients dropped out during the study period. Data were analyzed by repeated measured ANCOVA and the covariance was the dose of laxatives used for the two weeks. RESULTS: Frequency of defecation increased significantly and symptoms of constipation decreased significantly for patients in the experimental group. CONCLUSION: The study results suggest that the intake of carbonated water is an effective method for the intervention of constipation in elderly patients with CVA.
