A randomized, phase 1, placebo-controlled trial of APG-157 in oral cancer demonstrates systemic absorption and an inhibitory effect on cytokines and tumor-associated microbes.

BACKGROUND: Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG-157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target. METHODS: A double-blind, randomized, placebo-controlled, phase 1 clinical trial was conducted with APG-157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity. RESULTS: Treatment with APG-157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL-1ß, IL-6, and IL-8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T-cell recruitment to the tumor microenvironment. CONCLUSIONS: The results of the current study suggested that APG-157 could serve as a therapeutic drug in combination with immunotherapy. LAY SUMMARY: Curcumin has been shown to suppress tumor cells because of its antioxidant and anti-inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally. Subjects with oral cancer were given oral APG-157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue. APG-157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs.

A multidimensional meta-analysis of psychotherapy for PTSD.

OBJECTIVE: The authors present a multidimensional meta-analysis of studies published between 1980 and 2003 on psychotherapy for PTSD. METHOD: Data on variables not previously meta-analyzed such as inclusion and exclusion criteria and rates, recovery and improvement rates, and follow-up data were examined. RESULTS: Results suggest that psychotherapy for PTSD leads to a large initial improvement from baseline. More than half of patients who complete treatment with various forms of cognitive behavior therapy or eye movement desensitization and reprocessing improve. Reporting of metrics other than effect size provides a somewhat more nuanced account of outcome and generalizability. CONCLUSIONS: The majority of patients treated with psychotherapy for PTSD in randomized trials recover or improve, rendering these approaches some of the most effective psychosocial treatments devised to date. Several caveats, however, are important in applying these findings to patients treated in the community. Exclusion criteria and failure to address polysymptomatic presentations render generalizability to the population of PTSD patients indeterminate. The majority of patients posttreatment continue to have substantial residual symptoms, and follow-up data beyond very brief intervals have been largely absent. Future research intended to generalize to patients in practice should avoid exclusion criteria other than those a sensible clinician would impose in practice (e.g., schizophrenia), should avoid wait-list and other relatively inert control conditions, and should follow patients through at least 2 years.