A phase I trial of pre-operative radiotherapy for prostate cancer: Clinical and translational studies

作者：Supiot Stephane; Shubbar Shubber; Fleshner Neil; Warde Padraig; Hersey Karen; Wallace Kris; Cole Heather; Sweet Joan; Tsihlias John; Jewett Michael A S; Klotz Laurence; Bristow Robert G^*

来源：Radiotherapy and Oncology, 2008, 88(1): 53-60.

DOI：10.1016/j.radonc.2008.03.019

• pre-operative radiotherapy
• apoptosis
• senescence
• p21(WAF)
• radical prostatectomy
• p53
• cell cycte arrest

Background and purpose: Selected patients undergoing radical prostatectomy for localized prostate cancer can be at high-risk for pT3 disease and require subsequent radiotherapy. In a phase I trial, we investigated the feasibility of preoperative radiotherapy for this patient subset.
Materials and methods: Eligibility criteria were: T1/T2N0M0 tumors plus (i) Gleason >= 7, PSA > 10 ng/ml and < 35 ng/ml or (ii), PSA > 15 ng/ml and less < 35 ng/ml (any Gleason). Patients received 25 Gy in five fractions of radiotherapy followed by radical prostatectomy. Trial endpoints included intra-operative morbidity and late toxicity following combined treatment. We also stained pre- and post-radiotherapy prostate samples for DNA damage response proteins.
Results: Between 2001 and 2004, 15 patients were entered on trial. Thirteen patients completed combined-modality treatment. Only one patient had signs of intra-operative inflammation. No patient had post-operative complication. There was no severe late gastrointestinal toxicity. Late genitourinary toxicity consisted of severe urinary incontinence in 2 of 13 patients. From a translational standpoint, irradiated prostate tumor tissues had long-term activation of the CDK-inhibitor p21(WAF) associated with reduced cell proliferation.
Conclusion: Intra-operative morbidity is low following short-course, pre-operative radiotherapy. A phase II trial is planned to fully document biochemical response with this combined-modality approach.

• 出版日期2008-7