DOSE-ESCALATION STUDY OF RE-186 HYDROXYETHYLIDENE DIPHOSPHONATE IN PATIENTS WITH METASTATIC PROSTATE-CANCER

Rhenium-186 hydroxyethylidene diphosphonate (Re-186-HEDP) has been use d for the palliative treatment of metastatic bone pain. A phase 1 dose escalation study was performed using Re-186-HEDP. Twenty-four patient s with hormone-resistant prostate cancer entered the study. Each patie nt had at least four bone metastases and adequate haematological funct ion. Groups of at least three consecutive patients were treated with d oses starting at 1295 MBq and increasing to 3515 MBq (escalated in inc rements of 555 MBq). Thrombocytopenia proved to be the dose-limiting t oxicity, while leucopenia played a minor role. Early death occurred in one patient (10 days after administration) without clear relationship to the Re-186-HEDP therapy. Transient neurological dysfunction was se en in two cases. Two patients who received 3515 MBq Re-186-HEDP showed grade 3 toxicity (thrombocytes 25-50 x 10(9)/l), defined as unaccepta ble toxicity. After treatment alkaline phosphatase levels showed a tra nsient decrease in all patients (mean: 26% +/- 10% IU/l; range: 11%-44 %). Prostate-specific antigen values showed a decline in eight patient s, preceded by a temporary increase in three patients. From this study we conclude that the maximally tolerated dose of Re-186-HEDP is 2960 MBq. A placebo-controled comparative study on the efficacy of Re-186-H EDP has been initiated.