Current challenges and future perspectives in oral absorption research: An opinion of the UNGAP network

Although oral drug delivery is the preferred administration route and has been used for centuries, modern drug discovery and development pipelines challenge conventional formulation approaches and highlight the insufficient mechanistic understanding of processes critical to oral drug absorption. This review presents the opinion of UNGAP scientists on four key themes across the oral absorption landscape: (1) specific patient populations, (2) regional differences in the gastrointestinal tract, (3) advanced formulations and (4) food-drug interactions. The differences of oral absorption in pediatric and geriatric populations, the specific issues in colonic absorption, the formulation approaches for poorly water-soluble (small molecules) and poorly permeable (peptides, RNA etc.) drugs, as well as the vast realm of food effects, are some of the topics discussed in detail. The identified controversies and gaps in the current understanding of gastrointestinal absorption-related processes are used to create a roadmap for the future of oral drug absorption research

Induction chemotherapy followed by parenchyma-sparing surgery in medically inoperable NSCLC-results of a feasibility study

PURPOSE: Feasibility trial to test the toxicity and outcome of three cycles of induction chemotherapy followed by limited surgery in medically inoperable early stage NSCLC patients. PATIENTS AND METHODS: Thirteen patients with NSCLC (stages I-IIIB) with insufficient cardio-respiratory reserves for the oncologically required lung resection, received three cycles of induction chemotherapy with cisplatin (100mg/m(2)) and docetaxel (85mg/m(2)) followed by parenchyma-sparing lung surgery. Operability was evaluated with pulmonary function tests, perfusion scintigraphy and cardiopulmonary exercise testing. In selected patients coronary angiography or myocardial perfusion scintigraphy was performed. Rate of R0-resections was taken as primary outcome. RESULTS: Twelve of 13 patients received the three cycles of chemotherapy as planned. The main grade 3/4 hematological toxicity was neutropenia (62%), non-hematological toxicity was neutropenic fever (23%) and cough/dyspnea (31%). Complete, partial and stable responses to chemotherapy were seen in 1, 10 and 2 patients, respectively-the overall response rate was 85%. No patient had tumor progression. Eleven/13 (85% (CI 95% 54, 97) %) patients underwent surgery (4 lobectomies, 2 segmentectomies, and 5 wedge resections), all had a pathologically complete resection of the tumor. There was one postoperative death due to myocardial infarction. The median disease-free and overall survivals were 57(CI 95% 36-78) months and 66(CI 95% 40-92) months, with a median follow up time of 58 months. The 1-, 2- and 4-year OS was 85%, 85% and 67%, respectively. There were no significant changes in any lung function parameter compared to the preoperative assessment. The FEV(1) showed a trend for improved values after surgery. CONCLUSION: Induction chemotherapy in medically inoperable patients followed by parenchyma-sparing surgery is feasible and yields very promising results