HYPRO Trial Misses Acute Gastrointestinal Toxicity Non-Inferiority Criteria

Hypofractionated radiotherapy does not reduce the risk of acute gastrointestinal toxicity for men undergoing radiotherapy for intermediate- and high-risk prostate cancer

medwireNews: Hypofractionated radiotherapy for intermediate- or high-risk prostate cancer has failed to meet non-inferiority criteria for acute gastrointestinal toxicity in the phase III HYPRO trial when compared against standard fractionated radiation.

Hypofractionated radiotherapy consisted of 19 fractions of 3.4 Gy given three times a week for 6.5 weeks, whereas standard radiotherapy was given in 39 fractions of 2.0 Gy, 5 days a week over 8 weeks, explain Shafak Aluwini, from Erasmus MC Cancer Institute in Rotterdam, the Netherlands, and co-investigators.

The patients, all of whom had histologically confirmed T1b to T4 prostate cancer without confirmed nodal or distant disease, were followed-up for acute toxicity after 120 days, the team explains in The Lancet Oncology.

There was no significant difference between the 410 men in the hypofractionated and the 410 men in the standard protocol treatment groups with regard to the cumulative rate of grade 2 or more severe genitourinary toxicity (60.5 vs 57.8%) after 120 days of follow-up.

But the cumulative rate of grade 2 or more severe gastrointestinal toxicity was significantly higher in the hypofractionated group, at 42.0% versus 31.2% for the standard protocol group, giving a 10.8% difference which did not meet the non-inferiority criteria.

Grade 4 acute toxicity was rare in both groups, with genitourinary symptoms affecting one patient in each treatment group and no gastrointestinal cases reported.

At the 3-month checkpoint, grade 2 or more severe gastrointestinal toxicity was reported by 13.0% of both groups.

And grade 2 or more severe genitourinary toxicity had returned to baseline levels at this time point, affecting 23.0% of patients given the hypofractionated radiotherapy and 22.0% of patients given the standard protocol.

“This finding suggests that most acute genitourinary symptoms were reversible in both groups within 3 months after radiotherapy”, the researchers suggest.

The researchers note that compared with other hypofractionated radiotherapy studies, the HYPRO trial included more men with high-risk disease or grade 2 or more severe symptoms at baseline and older men, factors which predict acute genitourinary and/or gastrointestinal toxicity.

In an accompanying comment, David Dearnaley, from the Institute of Cancer Research in London, UK, writes that “[o]verall, the results are reassuring for hypofractionation” but notes that longer follow-up is required to determine whether acute gastrointestinal toxicity is associated with a risk of late treatment-related side effects.

Noting that the HYPRO and other hypofractionated trials are still to determine their primary survival endpoints, he concludes: “Oncologists and health commissioning groups need to be patient waiting for the efficacy results from these large phase 3 trials to mature before changing standard practice; however, if successful, hypofractionation will have major benefits for both patients and resource use.”


Aluwini S, Pos F, Schimmel E, et al. Hypofractionated versus conventionally fractionated radiotherapy for patients with prostate cancer (HYPRO): acute toxicity results from a randomised non-inferiority phase 3 trial. Lancet Oncol 2015; Online First 2 February. DOI: dx.doi.org/10.1016/S1470-2045(14)70482-6

Dearnaley DP. Hypofractionated radiotherapy in prostate cancer. Lancet Oncol 2015; Online First 2 February. DOI: dx.doi.org/10.1016/S1470-2045(15)70021-5

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