Small Molecular Subsets in Phase I Studies

Optimal sequential designs in phase I studies

Phase I clinical trials are conducted in order to find the maximum tolerated dose of a given drug out of a set of doses, usually finite. In general, once a formal target function and a suitable probability structure are defined, optimization of sequential studies can theoretically be achieved using backward induction. This is a computationally heavy task and most of the proposed methods can be ...

Studies in Molecular Dynamics. I. General Method

Overview of phase I/II pemetrexed studies.

Pemetrexed (Alimta) is an antifolate that is effective in the inhibition of multiple enzyme targets including thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase. The compound has been evaluated in several phase I trials, both as single agent and in combination with other cytotoxic agents. The initial schedule selected for further investigation in ph...

Lecithin - Stabilized Microemulsion: An Organogel for Topical Application of Ketorolac Tromethamine. I: Phase Behavior Studies

The partial phase behavior of systems composed of lecithin/isopropyl myristate (IPM)/water or ketorolac tromethamine (KT) solutions (2.5, 5, 10 and 50% w/w) at various lecithin/IPM weight ratios (km) have been investigated by the construction of phase diagrams. A commercially available soybean lecithin (namely, Epikuron 200, phosphatidylcholine purity greater than 95%) was used in this study. P...

Are Doses and Schedules of Small-Molecule Targeted Anticancer Drugs Recommended by Phase I Studies Realistic?

Tolerability of molecularly targeted agents (MTA) used in cancer therapeutics is determined in phase I trials. We reviewed the reported incidence of toxicity in phase III trials at doses and schedules recommended by phase I trials to evaluate whether these recommendations are realistic when drugs are used in larger populations of patients. We systematically reviewed a safety profile of small mo...