No side effect benefit for intermittent over continuous ADT
medwireNews: US researchers fail to find a benefit for intermittent over continuous androgen-deprivation therapy (ADT) with respect to the incidence of long-term adverse events in elderly men with prostate cancer.
Contrary to the study hypothesis, treatment with intermittent ADT did not lead to consistently fewer long-term side effects than continuous ADT, the researchers comment in JAMA Oncology. In fact, this analysis of the SWOG 9346 trial data showed that the incidence of ischaemic and thrombotic events was higher among men given intermittent ADT.
The team adds: “If these finding are confirmed, given the failure of the parent study to prove its noninferiority end point, clinicians should be cautious about using intermittent ADT therapy in older men with metastatic [prostate cancer] given our inability to demonstrate a reduction in long-term adverse health events, the primary rationale for intermittent ADT.”
In a linked commentary, Saroj Niraula (University of Manitoba, Winnipeg, Canada) and Ian Tannock (University of Toronto, Ontario, Canada) say that in light of the findings, “any advantage of intermittent ADT is likely to be limited to possible improvements in [quality of life] particularly during the off-treatment period; convenience of therapy; and savings in cost.”
Of the 1134 men with newly diagnosed, metastatic disease who were randomly assigned to receive either intermittent or continuous ADT in the SWOG 9346 trial, 636 men with a median age of 71.3 years were included in this analysis. Their Medicare claims records were evaluated to identify long-term adverse events, defined as at least two physician or outpatient claims a minimum of 30 days apart.
Researcher Dawn Hershman (Columbia University Medical Center, New York) and fellow investigators found that ADT-related complications were “common” in both the intermittent and continuous ADT groups, with hypercholesterolemia (31%) and osteoporosis (19%) observed most frequently in the overall study population.
But the treatment arms were comparable with respect to the 10-year cumulative incidence of four of the five groups of side effects assessed in the study – endocrine events, sexual dysfunction, dementia and depression, and acute renal injury.
However, the 10-year cumulative incidence of ischaemic or thrombotic events was significantly higher for the 325 men treated with intermittent ADT than for the 311 who received continuous ADT, at 33% versus 24%, a finding the researchers term “unexpected”.
The commentators note that both reductions in serum testosterone levels and testosterone supplementation have been linked with increased risk of cardiovascular events.
And they suggest: “Multiple insults to the coagulation system with decrease and increase in testosterone levels during intermittent ADT might therefore be responsible for the observations in the study.”
medwireNews is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016