No abstract

Diabetes contributes considerably to the health disparities in the Aboriginal population. To address the lack of Aboriginal-specific diabetes education tools, Feltman was designed for health professionals to deliver diabetes prevention and management information. This qualitative study aims to explore how this resource was used and its perceived effect on diabetes prevention and management in Victorian Aboriginal communities. Convenience sampling was used to recruit 18 participants (n=6 were Aboriginal) who had attended Feltman training between 2010 and 2016. Semi-structured interviews conducted via telephone or face-to-face were audio-recorded, transcribed and analysed via content analysis. Content analysis identified three main categories regarding Feltman: (1) utilisation in Aboriginal and mainstream health services; (2) as a comprehensive, engaging tool that supports understanding of diabetes; and (3) the barriers and challenges to Feltman’s use. Overall, Feltman was regarded as a culturally appropriate diabetes education tool that is visual, tactile, engaging, supportive of health literacy and perceived to enhance Community members’ understanding of diabetes prevention and management. This is the first study to provide insight into Feltman’s implementation; adding to the evidence-base for Aboriginal-specific diabetes education tools.

Tolerability of MM-310 & carboplatin combination and optimal scheduling Synergistic combination of MM-310 & carboplatin in Ovarian PDX model Platinum-taxane combinations are widely used to treat solid tumors either in first or later lines of therapy. While effective in many settings, platinum-taxane combinatorial regimens are limited by toxicities. We have recently developed an antibody directed nanotherapeutic (MM-310) encapsulating a docetaxel prodrug, targeted to Ephrin receptor A2 (EphA2). Preclinical investigation of MM-310 revealed that the liposomal formulation leads to prolonged docetaxel exposure of the tumor with decreased exposure of normal tissues leading to a shift in toxicity profile and potentially enabling more safe and effective combinations with platinum-based chemotherapeutics. In this study, we evaluated the activity of MM-310 in combination with carboplatin in several xenograft tumor models and compared it to the activity of free docetaxel in combination with carboplatin at equitoxic dosing. Tolerability of MM-310 in combination with carboplatin in mice was evaluated, including assessment of hepatotoxicity. Biodistribution, microdistribution, in vivo tumor growth, and mouse survival studies were performed in lung and ovarian cell line-derived (CDX) and patient-derived xenograft (PDX) models. MM-310 in combination with carboplatin was found to be well tolerated. Dosing both drugs at high doses showed maximum tolerability when the drugs were dosed three days apart. Carboplatin increased nanotherapeutic delivery to the tumor in a CDX model of triple negative breast cancer and in a PDX model of ovarian cancer. In vivo studies in lung and ovarian cancer xenograft models showed significant synergy between MM-310 and carboplatin in comparison to the monotherapies, as well as in comparison to free docetaxel with carboplatin, leading to a significant delay in tumor growth and increased survival (docetaxel/ carboplatin vs. MM-310/carboplatin, 0 vs 50% complete tumor regression, 24 vs 80 days median time to regrowth). Additionally, in the same studies, MM-310 combined with carboplatin was better tolerated than free docetaxel with carboplatin. Mechanistically, the synergistic anti-tumor activity of MM-310 with carboplatin may be partially due to a carboplatin mediated enhancement of nanotherapeutic delivery. The increased preclinical activity of the MM-310/carboplatin combination, together with the high tolerability following scheduling optimization tested in mice, makes this combination a promising regimen that warrants evaluation in clinical trials.

No abstract