Wednesday, November 25, 2009

Various positive data disclosed at AACR-NCI-EORTC meeting

Scientists, pharmaceutical companies and industry experts from around the world recently gathered at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held from 15th to 19th November, in Boston, MA, where much encouraging data were presented regarding a wide range of cancer indications. Of particular note, positive data were reported from studies in metastatic melanoma, lymphoma, and head and neck cancer.

Initial data from an ongoing Phase IIa study of Myriad Pharmaceuticals' Azixa (MPC-6827), a microtubule destabilising agent in Stage IV melanoma patients, demonstrated encouraging durations of response. The combination of Azixa at all concentrations with fixed-dose temozolomide, including the previously-determined single-agent maximum tolerated dose of Azixa, was safe and well tolerated. Ten patients achieved stable disease (SD) and two achieved confirmed partial responses (PRs). One patient had SD for four months before achieving a PR for an additional eight months. A second patient had SD for two months before achieving a PR for an additional four months.

Further, data from a Phase I study demonstrated that TopoTarget's belinostat (PXD101) in combination with Velcade (bortezomib) is well tolerated in patients with advanced solid tumours or lymphoma. A total of 22 were evaluable for toxicity and received a total of 58 treatment cycles. At the highest dose level, dose-limiting toxicity included Grade 4 thrombocytopenia and fatigue. Most adverse events (AEs) have been mild to moderate and four patients have maintained SD for four to six cycles of therapy.

Professor Peter Buhl Jensen, CEO of TopoTarget, commented: "we now know that full doses of belinostat can be given with full Velcade doses. This promising combination can now be tested in larger populations...belinostat may become an important treatment alone or may be part of an effective combination treatment as the safety profile of belinostat allows it to be combined in full dose with conventional and novel therapies like Velcade."

Separately, updated results from a Phase I/II trial (REO 011) of Oncolytics Biotech's Reolysin combined with carboplatin and paclitaxel (CP) for patients with advanced cancer, with a focus on H&N cancer, demonstrated that Reolysin was well tolerated when administered intravenously in combination with CP. Of 19 evaluable patients with H&N cancer, mostly squamous cell carcinoma of the H&N refractory to prior platinum-based chemotherapy for recurrent/metastatic disease, eight experienced PRs and six had SD. The total clinical benefit rate observed in H&N cancer patients in the trial was 74 per cent. Of four patients with malignant melanoma on the trial, one experienced a PR and one had SD.

Alice Rossiter - Cancer Drug News Editor

Wednesday, November 11, 2009

New direction needed for PC research

The current focus on individualised care in many different cancer indications has left pancreatic cancer (PC) behind. Patients diagnosed with this disease live no longer today than those diagnosed two decades ago, despite numerous amounts of clinical trials. Whilst there have been great advances in other cancers, with patients benefiting from targeted drugs such as Gleevec (imatinib) and Herceptin (trastuzumab), PC still remains aggressive as ever.

Published in the 26th October online edition of the Journal of Clinical Oncology (10.1200/JCO.2009.21.9022), an expert panel convened by the National Cancer Institute has issued a consensus report that discusses many aspects of developing and testing treatments in this disease, and charts a course for the next five years. The authors of the report have stressed that the recommendations be strongly considered in any clinical trial being planned for PC.

A recommendation is to design pilot studies that test potential treatments in smaller groups before proceeding to larger trials, which have previously yielded disappointing results. Decisions about which molecular targets and potential drugs to pursue will be made based on scientific evidence that will include preclinical and animal studies that better represent PC in humans.

As the report notes, a better understanding of the complex signalling pathways in pancreatic tumours and the role of the local tumour environment are needed. More sophisticated modelling systems and repositories of high-quality biological samples that can be shared among preclinical researchers are also essential. Published in the same issue the Journal of Clinical Oncology (10.1200/JCO.2009.24.2446), a study provides an example of the kinds of trials many in the field hope to avoid in the future. As has been the pattern for these studies, patients saw little or no benefit from the experimental treatment, in this case, a combination of gemcitabine and capecitabine, as compared with gemcitabine alone.

Scientists involved in clinical trials for PC are aware of the limited success, and have already begun to adopt new ideas about developing and testing treatments. Dr Philip A Philip, the report's senior author, commented: "we have to be more thoughtful and innovative in bringing forward new targeted therapies and treatment combinations." The hope is that the new strategy will ensure that resources and patient time are spent on the most promising treatments.

Separately, in findings that could help researchers focus their drug-development efforts, Massachusetts Institute of Technology cancer biologists have identified a subpopulation of cells that can give rise to PC. In mouse models, they also found that tumours can form in other, more mature pancreatic cell types, but only when they are injured or inflamed, suggesting that PC can arise from different types of cells depending on the circumstances. In future studies, the MIT researchers plan to use their mouse models to follow the molecular events that take place during PC development, and identify potential targets for drug treatments and protein markers for early diagnosis. These new mouse models could also help researchers test potential PC treatments.

Alice Rossiter - Cancer Drug News Editor