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A Phase I clinical trial to evaluate the safety of a new combination therapy for an aggressive type of brain tumor showed that the treatment was well tolerated by patients.
The trial used a combination of ADI-PEG20, pemetrexed and cisplatin, which showed encouraging efficacy in patients with recurrent high-grade glioma (HGG), a disease for which little progress has been made in recent years. decades.
As part of the trial, led by Professor Peter Szloserek of Queen Mary University of London and Barts Health NHS Trust, ten patients with extensively pretreated generalized hypoglycemia were treated with ADI-PEG20 in combination with chemotherapy. standard pemetrexed and cisplatin.
This clinical work builds on preclinical studies conducted by the Queen Mary's Barts Cancer Institute (funded by Cancer Research UK) and Imperial College London (funded in part by Brain Tumor Research), which revealed that ADI-PEG20 could enhance the effects of other standards. chemotherapies such as pemetrexed and cisplatin.
Normal cells are able to generate their own supply of arginine, an essential amino acid necessary for many cellular processes. However, this ability is lost in many types of tumors because of the decrease in the ASS1 enzyme required for arginine production. Therefore, the tumor cells depend on the intake of arginine in the blood, a vulnerability that can be exploited therapeutically. ADI-PEG20 works by reducing the depletion of arginine in the blood, which "starves" the tumors of this essential amino acid.
The badociation of the concept of arginine deprivation with pemetrexed and cisplatin has been shown to be effective in other types of cancer, including treatment-resistant AS1 deficient mesothelioma or non-cancerous lung cancer. small cells.
The results of the trial, published in Clinical Cancer Research, represent an important breakthrough for this historically underfunded area of research, for which the prognosis is very bleak and for which no standard reference treatment has been recognized.
Sue Farrington Smith, Executive Director of Brain Tumor Research, said, "Insufficient funding for research has prevented options and outcomes for brain tumor patients from aligning with other forms of cancer for which research is needed. The collaboration of two of our research centers shows that progress can be made and accelerates our efforts to work with the government and the largest cancer charities to ensure a better future for people with this condition. devastating disease and their families. "
Dr. Peter Hall, lead author of the study and lead registrar specializing in testing at the Barts Health NHS Trust, said: "This trial represents an important first step in the development of an approach. focused on biomarkers for the treatment of high-grade recurrent gliomas, a disease that has always been underfunded and for which the outlook remains very poor. "
As it was shown that the treatment was well tolerated by patients, the results of this trial pave the way for a Phase II trial including a larger cohort of patients for a more in-depth evaluation of efficacy, currently underway. development course.
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