DOI: 10.1007/s00259-017-3673-9Pages: 1-9

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

1. VU University Medical Centre, Department of Medical Oncology

2. Meander Medical Centre, Department of Medical Oncology

3. Meander Medical Centre, Department of Nuclear Medicine

4. University Medical Centre Utrecht, Department of Medical Oncology

5. VU University Medical Centre, Department of Radiology & Nuclear Medicine

6. Tergooi Medical Hospital, Department of Medical Oncology

7. St Antonius Hospital Utrecht, Department of Medical Oncology

8. Spaarne Gasthuis, Department of Medical Oncology

9. VU University Medical Centre, Department of Epidemiology and Biostatistics

10. Queen’s University Belfast, Centre for Cancer Research and Cell Biology

Correspondence to:
Joyce M. Dodewaard-de Jong
Tel: +31-(0)33-8502444
Email: jm.van.dodewaard@meandermc.nl

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Abstract

Background

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.

Methods

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.

Results

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%).

Conclusion

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.

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  • Accepted: Mar 3, 2017
  • Online: Apr 18, 2017

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