We are very pleased to have Dr Hammed Balogun acting as our guest host this month.
Dr Balogun will be reviewing “The effect of hepatic impairment on outcomes in phase 1 clinical trials in cancer subjects” (see below for more details) and will lead discussions with a small group of attendees.
This month's paper
The effect of hepatic impairment on outcomes in phase 1 clinical trials in cancer subjects.
Mansfield AS, Rudek MA, Vulih D, et al. Clin Cancer Res. 2016;22(22):5472-5479. doi:10.1158/1078-0432.CCR-16-0449
The NCI Cancer Therapy Evaluation Program sponsors hepatic dysfunction phase 1 clinical trials (HDCT) and phase 1 clinical trials (P1CT) to determine safe doses and schedules of antineoplastic therapeutics. We sought to compare clinical outcomes between these trial types while stratifying by hepatotoxic agents.
Individual subject data were extracted from the records of 51 NCI-sponsored HDCT and P1CT. The NCI’s Organ Dysfunction Working Group’s hepatic impairment categorization and two drug-induced liver injury (DILI) scales (FDA R ratio and Hy’s law) were used to classify subjects. The number of cycles administered and treatment discontinuation reason were also evaluated and compared between groups.
There were 513 and 1328 subjects treated on HDCT (n=9) and P1CT (n=42), respectively. There were differing patterns of DILI with significant worsening of total bilirubin in subjects on HDCT, and worsening of ALT in subjects on P1CT. Cholestatic peak patterns of liver impairment (predominant increases in alkaline phosphatase rather than transaminases) were more frequent in HDCT. Criteria for Hy’s Law were met by 11 subjects on P1CT but not by any subjects on HDCT. Disease progression was the most common reason for treatment discontinuation, followed by adverse events at similar frequencies in both HDCT and P1CT.
The differential effects on hepatotoxicity suggest that underlying hepatic function may affect susceptibility to and patterns of DILI. The incorporation of additional measures of hepatic function may help identify those at highest risk of hepatotoxicity in future trials since baseline liver tests did not.
About your host
Dr Balogun is a Pharmaceutical Physician with experience in early development drug safety, signal detection and safety evaluation. He has a background in general medicine and post graduate training in pharmacovigilance and Pharmacoepidemiology with interest in risk benefit evaluation.
Dr Balogun is also a PMST trainee with FPM. He currently works at Johnson and Johnson as an Associated Director of Global Medical Safety Operations Physician in the Oncology TA.
About journal clubs
Journal clubs are educational settings where individuals meet regularly to critically evaluate articles in the medical and scientific literature.
They are a recognised way of keeping up to date with latest advancements in areas of interest.
Queries: If you have any questions please email email@example.com.
Joining instructions will be emailed to registered attendees on the morning of the Journal Club. Please check you junk folder!
The views, information, or opinions expressed during FPM events and training are those of the individuals involved and do not necessarily represent those of the Faculty of Pharmaceutical Medicine. We value inclusivity, equality and diversity, and work hard to promote these whenever possible in all of our activities. We welcome your comments and feedback: firstname.lastname@example.org