Combination of celecoxib with percutaneous radiotherapy in patients with localised prostate cancer – a phase I study

BACKGROUND: Current approaches for the improvement of bNED for prostate cancer patients treated with radiotherapy mainly focus on dose escalation. However molecularly targeted approaches may also turn out to be of value. In this regard cyclooxygenase (COX)-2 inhibitors have been shown to exert some anti-tumour activities in human prostate cancer in vivo and in vitro. Although in vitro data indicated that the combination of COX-2 inhibition and radiation was not associated with an increased toxicity, we performed a phase I trial using high dose celecoxib together with percutaneous radiation therapy. METHODS: In order to rule out any increases of more than 20% incidence for a given side effect level 22 patients were included in the trial. Celecoxib was given 400 mg twice daily with onset of the radiation treatment. Risk adapted radiation doses were between 70 and 74 Gy standard fractionation. RTOG based gastrointestinal (GI) and genitourinary (GU) acute toxicity scoring was performed weekly during radiation therapy, at six weeks after therapy and three month after completing radiation treatment. RESULTS: Generally no major increase in the level and incidence of side effects potentially caused by the combined treatment was observed. In two cases a generalised skin rash occurred which immediately resolved upon discontinuation of the drug. No grade 3 and 4 toxicity was seen. Maximal GI toxicity grade 1 and 2 was observed in 85% and 10%, respectively. In terms of GU toxicity 80 % of the patients experienced a grade 1 toxicity and 10 % had grade 2 symptoms. CONCLUSION: The combination of irradiation to the prostate with concurrent high dose celecoxib was not associated with an increased level of side effects.