The Joplin Globe’s editor, Carol Stark, now keeps a journal that she will use to document her experiences as she becomes a participant in a Phase II trial of ADI-PEG 20 in combination with Gemcitabine and Docetaxel for the treatment of software tissue sarcoma.
Ms. Carl Stark is the editor of the Joplin Globe, a seven-day daily newspaper published in Joplin, Missouri—and an impressive person. She reports that nothing has worked as of yet—from standard treatment to surgery to other experimental medicines after two years of treatment. The tumors are spreading from the pelvic areas in a dangerous direction and she was consequently referred to Washington University St. Louis for specialist attention at the Siteman Cancer Center.
Ms. Stark notes that in the study the sponsors (Washington University St. Louis) will utilize two forms of standard chemotherapy in addition to a new investigational medicine called ADI-PEG 20. In this editorial, she shares how she is thinking about the trial and how the investigational therapy will work. She notes that the trial has been ongoing with potentially remarkable results.
Led by Washington University St. Louis Siteman Cancer Center, the study description first highlights that “the investigators have recently demonstrated that argininosuccinate synthase 1 (ASS1) expression is silenced 88% of all sarcomas (n =708), and that this loss is associated with a decreased overall survival.”
Using this extracellular arginine-depleting enzyme PEGylated arginine deiminase (ADI-PEG20), an extracellular arginine-depleting enzyme, the investigators demonstrated ADI-PEG20 induces a prosurvival metabolic reprogramming of ASS1-deficient sarcomas that redirects glucose into the serine/folate pathway directing the carbons from glucose into pyrimidine biosynthesis, thus sensitizing cells to death by the pyrimidine antimetabolite gemcitabine by using metabolomics.
The synthetic lethality was increased by the addition of docetaxel. Therefore, a Phase II clinical trial of ADI with gemcitabine and docetaxel, a standard line therapy for soft tissue sarcoma will be conducted to determine if the clinical benefit rate of gemcitabine and docetaxel is improved by the metabolic changes induced by ADI-PEG20.
The Study is designed to include 75 participants and runs to February 2025. The sponsor and central research site, Washington University, St. Louis also includes a couple of other sites including Stanford Medical Center and the Sarcoma Oncology Center in Santa Monica, CA.
Brian A. Van Time, MD, Ph.D. Other ADI-PEG 20 Research
A multinational research team from China and Taiwan studied ADI-PEG20 monotherapy and concluded it did not demonstrate an OS benefit in the second-line setting for HCC. It was well tolerated. They emphasized strategies to enhance prolonged arginine depletion and synergize the effect of ADI-PEG20 are on the way. Another multinational study concluded that ADI-PEG20 that the objective response rate (ORR) was 21% and median progression-free survival (PFS) was 7.3 months. Compared to other comparable data these figures were favorable.
The Patient Journey
Although Ms. Stark undoubtedly wouldn’t accept credit, she is a bold and courageous person for not only participating in this investigational research but also for coming out and discussing it in such an open way for others to understand—utilizing the forum and channel she has access to an editor for a newspaper. In what could be considered divisive times by many, she represents a common nexus of strength for us all, and while maintaining a sense of calm, cool and conviction while sharing how she thinks about this very complex science she must subject herself too- in prose that all of us can understand—even weaving in a sense of humor along the way. She faces a scary situation and an uncertain future (like the rest of us) and it would be very understandable to deal with it in other ways. Medicinal progress will only come about if people such as Carol Stark participate in research and share with others those experiences.Source: The Joplin Globe