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

Rhenium-186 hydroxyethylidene diphosphonate (Re-186-HEDP) has been used for the palliative treatment of metastatic bone pain. A phase 1 dose escalation study was performed using Re-186-HEDP. Twenty-four patients with hormone-resistant prostate cancer entered the study. Each patient had at least four bone metastases and adequate haematological function. Groups of at least three consecutive patients were treated with doses starting at 1295 MBq and increasing to 3515 MBq (escalated in increments of 555 MBq). Thrombocytopenia proved to be the dose-limiting toxicity, 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 seen 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 unacceptable toxicity. After treatment alkaline phosphatase levels showed a transient decrease in all patients (mean: 26% +/- 10% IU/l; range: 11%-44%). Prostate-specific antigen values showed a decline in eight patients, 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-HEDP has been initiated.