The integrin inhibitor cilengitide is to be used to treat patients suffering from glioblastoma, the most common type of malignant brain tumor
In the case of certain kinds of cancer, the need for new types of treatment is especially urgent. These include gioblastomas, the most common and most malignant of the brain tumors that affect adults. Former United States Senator Ted Kennedy, a particularly prominent patient, survived for a mere 15 months after his diagnosis, which was not much longer than the average. Such cases are incurable: Not only is it much more difficult to remove tumors surgically from the brain than from other organs, but the tumor cells are also resistant to radiation therapy, and the blood-brain barrier prevents the passage of many proven chemotherapeutic agents from the blood into the tissue of the tumor.
Is there such a thing as a tolerable cancer drug?
Treatment prospects were therefore fairly bleak for many decades. An early breakthrough did come with the development of the chemotherapeutic agent temozolomide, which initially extended the average survival time by between two and three months.
Yet chemotherapy also affects healthy cells and has adverse side effects that restrict its use. That’s why there is still an urgent need for more precisely targeted alternatives. When it comes to rare tumors such as glioblastoma which require a major research effort, there is generally a high level of collaboration between the various parties involved. Cilengitide is a prime example of a drug that is being developed by a pharmaceutical company — in this instance, Merck — in close cooperation with academic groups and is progressing even more successfully as a result.
Cilengitide has now entered Phase III trials, the decisive stage of drug development. Phase I trials are designed to assess tolerability; phase II tests the drug's efficacy and investigates different dosage requirements or therapy combinations. Results from this phase indicated longer survival times for patients treated with cilengitide in combination with radiation therapy and temozolomide. Furthermore, adverse side effects were remarkably rare.
These findings have persuaded Merck, along with the European Organisation for Research and Treatment of Cancer (EORTC) and clinical researchers, that the substantial effort and risks involved in conducting international, randomized Phase III trials will pay off. Patients participating in the randomized controlled CENTRIC trials are receiving either the standard therapy (surgery, radiation therapy, and temozolomide) or the standard therapy plus cilengitide.
The integrin inhibitor cilengitide is not the only substance investigated in the treatment of glioblastoma that blocks the supply of blood to tumors. Why is Professor Weller, one of the two heads of CENTRIC, so convinced by cilengitide? “In preliminary trials, other compounds were far less effective. But the biggest advantage of cilengitide is that it has very few side effects. There is nothing in the databases so far to suggest any serious adverse effects,” Weller explains, although he does qualify this with the observation that data from several thousand patients will have to be available before the drug's safety can be conclusively assessed.