Phase I trial for new targetted chemotherapy discussed at Geneva meeting

[Lani]

New way of inhibiting cell cycle shows promise

Geneva, Switzerland: A new anti-cancer compound that works by blocking a part of the cell's machinery that is crucial for cell division has shown promising results in a phase I clinical trial in patients who have failed to respond to other treatments. Now it is going forward into a phase II clinical trial programme. In addition, the compound will also be tested in combination with other anti-cancer drugs to see whether combined therapies could be even more effective.
Professor Patrick Schöffski told the 20th EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics in Geneva today (Wednesday 22 October) that after 50 patients had been given the compound BI 6727 in doses ranging from 12 to 450 mg, two patients with advanced bladder and ovarian cancers had shown confirmed partial responses and a further 32% of the patients had stable disease.
"The results so far indicate that BI 6727 is well tolerated by patients, with no serious side-effects detected. We have observed encouraging anti-tumour activity, which we would not necessarily expect to see in a phase I trial, and which warrants investigation in further clinical trials," said Prof Schöffski, who is professor of medical oncology and head of the Department of General Medical Oncology at the University Hospitals Leuven (Belgium). [2]
BI 6727 is one in a series of compounds developed by Boehringer Ingelheim that work by inhibiting the action of a protein called Polo-like kinase 1 (Plk1), high levels of which are present in human tumours, but not in normal tissue. Plk1 is involved in cell growth; inhibiting it leads to abnormal mitotic spindles - the structures that separate the chromosomes into daughter cells during cell division - and this disrupts cell division, inhibiting the growth of tumour tissue.
"Plk1 inhibitors are targeted, cell cycle blockers that lead to spindle defects by inhibiting a key regulator of mitosis. They act on the mitotic spindle in a completely different manner compared to established anti-cancer agents such as vinca alkaloids or taxanes that directly bind to structural components of the mitotic spindle. Due to high levels of Plk1 in tumour cells compared to surrounding healthy tissue, compounds such as BI 6727 are effectively targeting dividing cancer cells," said Prof Schöffski. "The results from this phase I trial suggest that BI 6727 potentially is a 'first in class' Plk1 inhibitor and the anti-tumour activity we have seen supports Plk1 as a therapeutic target."