Hypofractionated Radiotherapy Not Noninferior to Standard Radiotherapy in Acute Toxicity in Phase III Prostate Cancer Trial
In the Dutch phase III HYPRO trial reported in The Lancet Oncology, Aluwini et al found that hypofractionated radiotherapy was not noninferior to standard fractionated radiotherapy in acute genitourinary and gastrointestinal toxicity in men with intermediate- or high-risk prostate cancer. Efficacy results are awaited.
Study Details
In the trial, 820 patients aged 44 to 85 years from seven centers in the Netherlands were randomly assigned between March 2007 and December 2010 to receive hypofractionation (n = 410) or standard fractionation radiotherapy (n = 410). Patients had stage T1b-T4, NX-0, MX-0 disease and prostate-specific antigen level ≤ 60 ng/mL. Hypofractionation consisted of 19 fractions of 3.4 Gy in 6.5 weeks (3 fractions per week), and standard fractionation consisted of 39 fractions of 2 Gy in 8 weeks (5 fractions per week). The primary endpoint is 5-year relapse-free survival. Noninferiority of hypofractionation was tested for genitourinary and gastrointestinal acute toxicity, with the null hypothesis that the cumulative incidence of each type of adverse event would not be > 8% higher in the hypofractionation group.
Toxicity Rates
At 3 months after radiotherapy, grade ≥ 2 genitourinary toxicity was reported in 23% of patients in the hypofractionation group vs 22% in the standard fractionation group, and grade ≥ 2 gastrointestinal toxicity was reported in 13% vs 13%. Grade 4 genitourinary toxicity occurred in 1 patient (<1%) in each group, and no grade 4 gastrointestinal toxicity was observed.
At 120 days, the cumulative incidence of grade ≥ 2 acute genitourinary toxicity was 60.5% in the hypofractionation group vs 57.8% in the standard fractionation group (odds ratio [OR] = 1.12, P = .43), and the cumulative incidence of grade ≥ 2 acute gastrointestinal toxicity was 42.0% vs 31.2% (OR = 1.6, P = .0015; noninferiority not confirmed). Grade 3 genitourinary toxicity occurred in 20.3% vs 17.6% (P = .34); grade 4 genitourinary toxicity occurred in one patient in each group. Grade 3 gastrointestinal toxicity occurred in 5.7% vs 4.6% (P = .48), with no grade 4 events being observed.
The investigators concluded: “Hypofractionated radiotherapy was not noninferior to standard fractionated radiotherapy in terms of acute genitourinary and gastrointestinal toxicity for men with intermediate-risk and high-risk prostate cancer. In fact, the cumulative incidence of grade 2 or worse acute gastrointestinal toxicity was significantly higher in patients given hypofractionation than in those given standard fractionated radiotherapy. Patients remain in follow-up for efficacy endpoints.”
Shafak Aluwini, MD, of Erasmus Medical Center Cancer Institute, is the corresponding author for the Lancet Oncology article.
The study is funded by the Dutch Cancer Society. The study authors reported no potential conflicts of interest.
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