Late dosing of common luteinizing hormone-releasing hormone (LHRH) agonists used for androgen deprivation therapy (ADT) in prostate cancer occurs frequently, a researcher reported.
Late dosing was particularly common (over 80%) when measured against the 28-day dosing schedules used in clinical trials for these therapies, and found in prescribing information, according to Julia Vandross, NP-BC, BSN, MSN, of Providence Saint John’s Health Center in California.
The findings were presented in an e-poster at the Oncology Nursing Society virtual meeting, and recently published in The Journal of Urology.
“Achieving and maintaining effective testosterone suppression to levels attained with surgical castration is the cornerstone of ADT for advanced prostate cancer,” pointed out Vandross and colleagues. However, testosterone levels can rise above castrate level (50 ng/dL) between injections, particularly if those injections are administered late, they added.
The authors conducted an observational analysis of the records of prostate cancer patients who received one of two different forms of leuprolide acetate, the most commonly used LHRH agonist in the U.S. — GEL-LA, an in situ-gel technology delivered subcutaneously; and Msphere-LA, a microsphere technology delivered by intramuscular injection.
They used two definitions of months — a 28-day month in which late was defined as dosing after day 28, 84, 112, or 168 for 1-, 3-, 4-, and 6-month formulations. However, they noted that scheduling of ADT is likely based on calendar months under the assumption that efficacy extends beyond labeling instructions. Thus, the authors added approximately four days per month and defined late as dosing after day 32, 97, 128, or 194.
A total of 10,398 patients received either of the two therapies — 2,038 receiving Gel-LA and 8,360 getting Msphere-LA. Vandross and colleagues reported that for a 28-day month, 80% and 86% were late with the two therapies, respectively, while 27% were late for both with the extended-month definition.
The authors stated that testosterone levels were high with late injections regardless of which therapy was used. However, they also noted that all Gel-LA formulations demonstrated lower mean testosterone levels and lower rates of testosterone above 50 ng/dL or above 20 ng/dL than Msphere-LA.
For example, GEL-LA demonstrated lower proportions of testosterone breakthroughs than Msphere-LA for late injections. For a 28-day month, 14% of Msphere-LA testosterone tests compared to 10% of Gel-LA testosterone tests were above 50 ng/dL (OR 1.5, 95% CI 1.2-1.9), while for an extended month 25% compared to 18%, respectively, were above 50 ng/dL (OR 1.5, 95% CI 1.1-2.0).
And one-third of Msphere-LA testosterone tests were above 20 ng/dL compared to one-quarter of Gel-LA testosterone tests for a 28-day month (OR 1.5, 95% CI 1.3-1.8), while rates were 44% and 34%, respectively, for the extended month (OR 1.5, 95% CI 1.2-1.9).
For late injections, GEL-LA patients had significantly lower mean testosterone levels than Msphere LA patients for both the 28-day month (34 ng/dL and 46 ng/dL, respectively) and the extended month (48 ng/dL and 76 ng/dL).
From a nursing perspective, Vandross and colleagues noted that since higher levels of testosterone, including testosterone escapes, can adversely affect prostate cancer disease progression, as well as survival, “nurses should ensure dosing schedule compliance, recommend an ADT that optimizes [testosterone] suppression, and educate patients on the importance of adherence to labelled dosing periods.”
“ADT is the foundation we build on for the treatment of advanced prostate cancer,” co-author E. David Crawford, MD, of the University of California San Diego, told MedPage Today.
Crawford observed that the trials that resulted in FDA approvals were based on 28-day dosing or multiples of that for 3-, 4-, and 6-month dosing. Yet “84% of injections given as documented in our analysis of over 22,000 administered were late,” he pointed out.
“We demonstrated that there were testosterone escapes and also PSA rises,” said Crawford. “We need to follow guidelines.”
The study was funded by Tolmar Pharmaceuticals.