The old and the new: Improving paclitaxel-based therapy...advances in HDAC inhibitors

DailyUpdates 6th June: As ASCO continues in full swing, we again focus on oncology. Today's edition of DailyUpdates includes 10 new papers on oncology research plus a further 20 or so press releases from companies presenting at ASCO. This is of course in addition to the rest of our content from across the drug development sector (see it all here). Today's headline paper unerpins the intriguing idea that the premedication required prior to Taxotere administration may significantly limit its efficacy. Intreresting reading for Sanofi-Aventis as well as APP, makers of Abraxis. The headline news item comes from Merck and focuses on the advance of their HDAC inhibitor

Improving paclitaxel-based therapy: Paclitaxel (Taxotere) is a widely used naturally occurring antineoplastic agent that has shown great promise in the treatment of a variety of human solid tumors, particularly for advanced breast and ovarian cancers. Recent studies have suggested that glucocorticoids may inhibit paclitaxel-induced apoptosis and since glucocorticoids are commonly used prior to chemotherapy this issue is critical. Today's featured study confirms this interaction reporting that paclitaxel-induced apoptosis may be reduced by as much as 25% by premedication. The Taxotere market is entering a dynamic period with its upcoming patent expiry and the recent launch of ABRAXANE (see Commercial Insight: Cytotoxics). ABRAXANE is a novel, albumin-bound formulation of paclitaxel approved by the FDA in January 2005. In a randomized Phase III study in women with metastatic breast cancer who had failed prior combination chemotherapy, ABRAXANE demonstrated a significantly higher response rate than standard paclitaxel (Gradishar et al, 2005). In this study ABRAXANE was administered without pre-medication as hypersensitivity reaction are not a problem with this agent; in contrast paclitaxel-administered patients were pre-medicated. Response rates were 39% and 19% respectively and we ask whether this was more related to the negative effect of the premedication than a benefit of ABRAXANE per se; likewise we ask whether Sanofi-Aventis should increase their emphasis on studying the efficacy of Taxotere in the context of different premedications in order to protect sales of this chemotherapy which was worth 1.6 billion euros in 2005. Comments? Go to our Drug Development Forum

Pivotal data published demonstrating efficacy of HDAC inhibitor: The field of histone deacetylase inhibitors is moving into a new phase of development (see Histone deacetylase inhibitors-Moving from the bench to a promising companion for classic and targeted cancer therapies). The exponential growth in the level of research activity surrounding the histone deacetylases witnessed over the past decade has now started to produce success in the clinic, particularly in the field of oncology. The most advanced therapeutic candidates such as SAHA and FK228 are already showing promising activity and today's highlighted press release features the former, also known as ZOLINZA (vorinostat). Merck, who expect to file the NDA for ZOLINZA in Cutaneous T-cell Lymphoma with the FDA this year, yesterday announced pivotal phase IIb data reporting that ZOLINZA produced an objective response in 30% of patients with advanced, refractory cutaneous T-cell lymphoma. This condition is an orphan condition affecting just 20,000 patients in the US; the data are crucial however not only to these patients but also more generally as proof of concept is provided to support a broad body of studies currently underway with other HDAC inhibitors and in other malignancies.