by ecancer reporter Janet Fricker

In two separate phase III studies, reported in the International Journal of Radiation Oncology Biology Physics, hypofractionated radiotherapy was found to have superior efficacy to conventional dose schedules of radiotherapy of prostate cancer.  One study recruited patients with high risk prostate cancer, while the other recruited patients with localised carcinoma of the prostate.

Radiotherapy represents one of best established therapies for prostate cancer. Currently patients are required to attend daily treatments over seven to eight weeks, which can be both costly and disruptive to patient’s lives, especially for those who live some distance from the treatment centre.   A new approach is hypofractionated radiation therapy that involves delivering higher individual doses of radiation over a smaller number of treatments, resulting in the overall delivery of a biologically equivalent dose of radiation. It is hoped that adoption of the approach would result in reduced treatment costs, less distress to the patient and shorter waiting periods. Until now, however, only two randomised studies have been published evaluating the efficacy and toxicity of hypofractionated versus conventionally fractionated dose schedules.

In the first study, undertaken by Giorgio Arcangeli and colleagues from Regina Elena National Cancer Institute (Rome, Italy), 168 patients with high-risk prostate cancer were randomised between January 2003 and December 2007, to receive either hypofractionated  (62 Gy in 20 separate fractions over 5 weeks) or conventional schedules (80Gy in 40 fractions over 8 weeks) for 3 D conformal radiotherapy (1).

Results show that 3-year freedom from biochemical failure rates were 87% in the hypofractionated arm versus 79 % in the conventional fractionation group (p=0.035). No difference was found for late toxicity between the two treatment groups, with 3-year Grade 2 rates of 17% and 16% for gastrointestinal and 14% and 11% for genitourinary in the hypofractionation and conventional fractionation groups respectively.

“The significant improvement of biochemical response observed with hypofractionation supports the radiobiological assumptions of the high sensitivity of prostate tumours to large dose fractions. Whether this biochemical improvement will translate into better clinical long-term results requires additional study,” write the authors

In the second study by Eric Yeoh and colleagues, from the Royal Adelaide Hospital (Adelaide, Australia), randomised 217 patients with localized carcinoma of the prostate to the hypofractionated (55 Gy in 20 fractions over four weeks, n=108) or the conventional (64Gy in 32 fractions over 6.5 weeks, n=109) dose schedules and followed them for a median of 90 months (2). 

Results show that the biochemical relapse-free rate was 53% in the hypofractionated group versus 34% in the conventional schedule. Gastro intestinal and genitourinary toxicity did not differ between the two dosing schedules.

“The absence of significant differences in the clinical end-points between the hypofractionated and conventional dose schedules, such as overall survival (71% versus 69%) and hormonal-free survival (78% versus 76%), probably reflected the lack of statistical power in detecting these changes, compounded by the deaths from unrelated causes,” write the authors.

Commenting on both studies, Dr Barbara Jereczek, from the European Institute of Oncology (Milan, Italy), said, ”Hypofractionation is a commonly used modern approach based on imaging guided technologies, but very little randomised evidence is available at the moment. So these trials give us important evidence on the benefits of such an approach. There are currently several other ongoing trials on this subject, so in the near future we should have more clear insight into hypofractionation.”

References

1.       G Arcangeli, B Saracino, S Gomellini et al. A prospective Phase III randomised trial of hypofractionation versus conventional fractionation in patients with high-risk prostate cancer. Int. J. Radiation Oncology Biol. Phys. 2010. 78, 11-18.

2.       E Yeoh, R Rotten, and J Butters et al. Hypofractionated versus conventionally fractionated radiotherapy for prostate carcinoma: final results of phase III randomised trial. Ibid, 1-8.