RESUMO
BACKGROUND: Pomegranate juice has been associated with PSA doubling time (PSADT) elongation in a single-arm phase II trial. This study assesses biological activity of two doses of pomegranate extract (POMx) in men with recurrent prostate cancer, using changes in PSADT as the primary outcome. METHODS: This randomized, multi-center, double-blind phase II, dose-exploring trial randomized men with a rising PSA and without metastases to receive 1 or 3 g of POMx, stratified by baseline PSADT and Gleason score. Patients (104) were enrolled and treated for up to 18 months. The intent-to-treat (ITT) population was 96% white, with median age 74.5 years and median Gleason score 7. This study was designed to detect a 6-month on-study increase in PSADT from baseline in each arm. RESULTS: Overall, median PSADT in the ITT population lengthened from 11.9 months at baseline to 18.5 months after treatment (P < 0.001). PSADT lengthened in the low-dose group from 11.9 to 18.8 months and 12.2 to 17.5 months in the high-dose group, with no significant difference between dose groups (P = 0.554). PSADT increases >100% of baseline were observed in 43% of patients. Declining PSA levels were observed in 13 patients (13%). In all, 42% of patients discontinued treatment before meeting the protocol-definition of PSA progression, or 18 months, primarily due to a rising PSA. No significant changes occurred in testosterone. Although no clinically significant toxicities were seen, diarrhea was seen in 1.9% and 13.5% of patients in the 1- and 3-g dose groups, respectively. CONCLUSIONS: POMx treatment was associated with ≥ 6 month increases in PSADT in both treatment arms without adverse effects. The significance of this on-study slowing of PSADT remains unclear, reinforcing the need for placebo-controlled studies in this patient population.
Assuntos
Antineoplásicos/administração & dosagem , Lythraceae , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/sangueRESUMO
The clinical safety, use and pharmacokinetics of a new needle-free device for delivery of growth hormone (GH) were compared with those of conventional needle injection devices. In an open-label, randomized, 4-period crossover study, 18 healthy adults received single subcutaneous injections of Genotropin administered by the Genotropin ZipTip needle-free device and by conventional injection. Bioequivalence was established between the devices. In a separate open-label, randomized, multicenter, 2-period crossover study, pediatric patients underwent 2-weeks Genotropin treatment administered by the Genotropin ZipTip and by a fine-gauge needle device (>95% used the Genotropin Pen). In total, 128/133 patients who were treated completed the study. Genotropin ZipTip was well tolerated and >50% of patients found no difference between the devices for all parameters assessed. After study completion, >20% patients preferred to continue using Genotropin ZipTip. Although statistical analyses demonstrated superiority of the Genotropin Pen versus Genotropin ZipTip for bleeding, pain, soreness, and bruising, Genotropin ZipTip was considered to provide a safe and bioequivalent alternative to needle injection.
Assuntos
Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/farmacocinética , Injeções a Jato/efeitos adversos , Injeções Subcutâneas/instrumentação , Adolescente , Adulto , Criança , Pré-Escolar , Contusões/etiologia , Contusões/prevenção & controle , Estudos Cross-Over , Feminino , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Injeções a Jato/instrumentação , Injeções Subcutâneas/efeitos adversos , Masculino , Aceitação pelo Paciente de Cuidados de Saúde , Valores de Referência , Equivalência TerapêuticaRESUMO
The use and availability of over-the-counter (OTC) medication is increasing. Although regulatory agencies take care to assure than nonprescription medications are safe and effective, these drugs still have the potential to have clinically significant interactions with prescription medicines. The major classes of OTC medication to be considered in this light include antacids, histamine H2 receptor antagonists, NSAIDs, cough and cold preparations and the antiasthma products. Healthcare providers and patients/consumers should be educated regarding possible drug interactions, patient drug regimens should be simplified where possible, and all therapeutic failures and adverse reactions should be investigated with regard to the potential contribution of OTC drug products. Regulatory agencies and pharmaceutical manufacturers should ensure that nonprescription drug labelling is complete and intelligible to meet these objectives. Consideration should be given to improving the postmarketing surveillance of OTC medications.