A randomised, phase II study of repeated rhenium-188-HEDP combined with docetaxel and prednisone versus docetaxel and prednisone alone in castration-resistant prostate cancer (CRPC) metastatic to bone; the Taxium II trial.

Rhenium-188-HEDP is a beta-emitting radiopharmaceutical used for palliation of metastatic bone pain. We investigated whether the addition of rhenium-188-HEDP to docetaxel/prednisone improved efficacy of chemotherapy in patients with CRPC.

Patients with progressive CRPC and osteoblastic bone metastases were randomised for first-line docetaxel 75 mg/m2 3-weekly plus prednisone with or without 2 injections of rhenium-188-HEDP after the third (40 MBq/kg) and after the sixth (20 MBq/kg) cycle of docetaxel. Primary endpoint was progression-free survival (PFS), defined as either PSA, radiographic or clinical progression. Patients were stratified by extent of bone metastases and hospital.

Forty-two patients were randomised for standard treatment and 46 patients for combination therapy. Median number of cycles of docetaxel was 9 in the control group and 8 in the experimental group. Median follow-up was 18.4 months. Two patients from the experimental group did not start treatment after randomisation. In the intention to treat analysis no differences in PFS, survival and PSA became apparent between the two groups. In an exploratory per-protocol analysis median overall survival was significantly longer in the experimental group (33.8 months (95%CI 31.75-35.85)) than in the control group (21.0 months (95%CI 13.61-28.39); p 0.012). Also median PFS in patients with a baseline phosphatase >220U/L was significantly better with combination treatment (9.0 months (95%CI 3.92-14.08) versus 6.2 months (95%CI 3.08-9.32); log rank p 0.005). As expected, thrombocytopenia (grade I/II) was reported more frequently in the experimental group (25% versus 0%).

Combined treatment with rhenium-188-HEDP and docetaxel did not prolong PFS in patients with CRPC. The observed survival benefit in the per-protocol analysis warrants further studies in the combined treatment of chemotherapy and radiopharmaceuticals.

European journal of nuclear medicine and molecular imaging. 2017 Apr 18 [Epub]

Joyce M van Dodewaard-de Jong, John M H de Klerk, Haiko J Bloemendal, Daniela E Oprea-Lager, Otto S Hoekstra, H Pieter van den Berg, Maartje Los, Aart Beeker, Marianne A Jonker, Joe M O'Sullivan, Henk M W Verheul, Alfons J M van den Eertwegh

Department of Medical Oncology, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. ., Department of Nuclear Medicine, Meander Medical Centre, Maatweg 3, 3813 TZ, Amersfoort, The Netherlands., Department of Medical Oncology, Meander Medical Centre, Maatweg 3, 3813 TZ, Amersfoort, The Netherlands., Department of Radiology & Nuclear Medicine, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands., Department of Medical Oncology, Tergooi Medical Hospital, Van Riebeeckweg 212, 1213 XZ, Hilversum, The Netherlands., Department of Medical Oncology, St Antonius Hospital Utrecht, Soestwetering 1, 3543 AZ, Utrecht, The Netherlands., Department of Medical Oncology, Spaarne Gasthuis, Spaarnepoort 1, 2134 TM, Hoofddorp, The Netherlands., Department of Epidemiology and Biostatistics, VU University Medical Centre, De Boelelaan 1089a, 1081 HV, Amsterdam, The Netherlands., Centre for Cancer Research and Cell Biology, Queen's University Belfast, Lisburn Road, Belfast, BT9 7AB, Northern Ireland, UK., Department of Medical Oncology, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.