Clinical benefit of bone-targeted radiometabolic therapy with 153Sm-EDTMP combined with chemotherapy in patients with metastatic hormone-refractory prostate cancer.

Bone metastases are responsible for most of the morbidity associated with hormone-refractory prostate cancer (HRPC). ¹⁵³Sm-ethylenediaminetetramethylene phosphonate (¹⁵³Sm-EDTMP) has been approved for palliation of painful skeletal metastases. We retrospectively investigated the possible synergistic effect on survival of ¹⁵³Sm-EDTMP (given to HRPC patients for bone pain palliation) and chemotherapy. Forty-five HRPC patients were evaluated, with a median age of 71 years. The number of metastatic bone sites was ≤10 in 25 patients and >10 in 20 patients. Median serum PSA was 224 ng/ml. Bone pain was mild in 6 patients, moderate in 16, severe in 22 and intolerable in 1. Fifteen patients were only treated with ¹⁵³Sm-EDTMP (group A), while 30 patients also received chemotherapy (estramustine phosphate or mitoxantrone plus prednisone) at variable times: between 3 and 5 months after ¹⁵³Sm-EDTMP (14 patients, group B) or within 1 month after ¹⁵³Sm-EDTMP (16 patients, group C). Haematological toxicities observed after either regimen were in general mild, consistent with common observations after either ¹⁵³Sm-EDTMP or chemotherapy, and without any additive adverse effects in the patients receiving both ¹⁵³Sm-EDTMP and chemotherapy. Bone pain palliation to some degree was induced by ¹⁵³Sm-EDTMP in 32/45 patients (71.1%), the proportion of patients with a favourable clinical response being significantly higher in group C than in group A (87.5% vs 53.3%, p = 0.0388). Also in terms of biochemical response (serum PSA levels), patients of group C performed significantly better than patients of group A ( p = 0.0235). Overall median survival from the time of administration of ¹⁵³Sm-EDTMP was 15 months in the total cohort of 45 patients, and was significantly longer in group C than in either group B (30 months vs 11 months, p = 0.023) or group A (30 months vs 10 months, p = 0.008). The results of this study confirm that ¹⁵³Sm-EDTMP is effective in terms of pain relief and PSA response, with minimal toxicity. When it was administered in combination with chemotherapy, prolonged survival indicated actual clinical benefit, while there were no additive toxicities. These results provide the rationale for future prospective evaluation of combined therapeutic strategies. [ABSTRACT FROM AUTHOR]