Cardio-Oncology: Where Safety Pharmacology Fits In
Earlier this month I attended an excellent Safety Pharmacology Society regional meeting at Pfizer-La Jolla focused on cardio-oncology and safety pharmacology.
Dr. Lori Minasian, Chief of the Community Oncology and Prevention Trials Research Group Program and the National Cancer Institute of the National Institutes of Health (NIH), opened the conversation by reminding us we should feel some sense of accomplishment at being able to worry about the cardiovascular side effects of cancer treatment. She pointed out that in the not too distant past, chemotherapy had not generally been associated with levels of efficacy that would provide either time or a framework for such concern.
She pointed out that we are now in a new age where targeted and specific drugs are increasing survival with fewer toxic side effects – allowing us to have the “luxury” of holding such discussions. (Her clinician – and patient – perspective was a welcomed perspective that is often missing from these seminars and scientific meetings.)
Substantive data from case studies of compounds in this ‘new age’ were examined, including VEGF and MEK inhibitors among others.
In general we are concerned about downstream effects of hypertension and cardiac dysfunction, with a pinch of QT prolongation for good measure. More on cardiovascular toxicity in cancer drugs.
The regulatory and industrial perspectives on how to handle these issues were covered at the meeting as well. Dr. Darrell Abernathy from the USFDA detailed thoughts on using a “systems pharmacology” approach for predicting and evaluating cardiac safety signals. Scientists from Pfizer and Novartis discussed their testing schemes that included preclinical models such as Langendorff isolated hearts, telemetry and echocardiography.
- The cardiovascular effects of these newer anti-cancer agents can be modeled in a preclinical fashion.
- The more we know about the multi-faceted profile of these agents, the better chance we have to simultaneously treat the disease while working to mitigate any side effects.