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

Multimodality Treatment for Early-Stage Hepatocellular Carcinoma: A Bridging Therapy for Liver Transplantation

Purpose: To evaluate the efficiency of a multimodality approach consisting of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) as bridging therapy for patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT) and to evaluate the histopathological response in explant specimens. Materials and Methods: Between April 2001 and November 2011, 36 patients with 50 HCC nodules (1.4-5.0 cm, median 2.8 cm) on the waiting list for liver transplantation were treated by TACE and RFA. The drop-out rate during the follow-up period was recorded. The local efficacy was evaluated by histopathological examination of the explanted livers. Results: During a median follow-up time of 29 (4.0-95.3) months the cumulative drop-out rate for the patients on the waiting list was 0, 2.8, 5.5, 11.0, 13.9 and 16.7% at 3, 6, 12, 24, 36 and 48 months, respectively. 16 patients (with 26 HCC lesions) out of 36(44.4%) were transplanted by the end of study with a median waiting list time of 13.7 (2.5-37.8) months. The histopathological examination of the explanted specimens revealed a complete necrosis in 20 of 26 HCCs (76.9%), whereas 6 (23.1%) nodules showed viable residual tumor tissue. All transplanted patients are alive at a median time of 29.9 months. Imaging correlation showed 100% specificity and 66.7% sensitivity for the depiction of residual or recurrent tumor. Conclusion: We conclude that TACE.combined with RFA could provide an effective treatment to decrease the drop-out rate from the OLT waiting list for HCC patients. Furthermore, this combination therapy results in high rates of complete tumor necrosis as evaluated in the histopathological analysis of the explanted livers. Further randomized trials are needed to demonstrate if there is a benefit in comparison with a single-treatment approach. copyright (C) 2012 S. Karger AG, Base