Dose escalation study with rhenium-188 hydroxyethylidene diphosphonate in prostate cancer patients with osseous metastases

The aim of this study was to determine the maximum tolerated dose of rhenium-188 hydroxyethylidene diphosphonate (HEDP) in prostate cancer patients with osseous metastases who are suffering from bone pain, Twenty-two patients received a single injection of escalating doses of carrier-added Re-188-HEDP [1.3 GBq (35 mCi), 2.6 GBq (70 mCi), 3.3 GBq (90 mCi) and 4.4 GBq (120 mCi)]. Blood counts and biochemical parameters were measured weekly over a period of 8 weeks. Haematological toxicity (WHO grading) of grade 3 or 4 was considered unacceptable. Clinical follow-up studies including methods of pain documentation (medication, pain diary) were performed for 6 months after treatment, In the 1.3-GBq group. no haematological toxicity was observed. First haematotoxic results were noted in those patients with a dose of 2.6 GBq Re-188-HEDP. In the 3.3-GBq group, one patient showed a reversible thrombopenia of grade 1, one a reversible thrombopenia of grade 2 and three a reversible leukopenia of grade 1. In the 4.4-GBq group, thrombopenia of grades 3 and 4 was observed in one and two patients (baseline thrombocyte count <200 x 10(9)/l), respectively, and leukopenia of grade 3 was documented in one patient. The overall nadir of thrombopenia was at week 4. The individual, maximum percentage decrease in thrombocytes in the 1.3-, 2.6-, 3.3- and 4.4-GBq groups was 17%, 40%, 60% and 86%, respectively. In two patients, a transient increase in serum creatinine was observed (max, 1.6 mg/dl). Pain palliation was reported by 64% of patients, with a mean duration of 7.5 weeks. The response rate seemed to increase with higher doses, reaching 75% in the 4.4-GBq group, It is concluded that in prostate cancer patients, the maximum tolerated dose of Re-188-HEDP is 3.3 GBq if the baseline thrombocyte count is below 200x10(9)/l, In patients with thrombocyte counts significantly above 200x10(9)/1, a dose of 4.4 GBq might be tolerable, Thrombo- and leukopenia are the most important side-effects, Pain palliation can be achieved in 60%-75% of patients receiving a dose of 2.6 GBq or more of Re-188-HEDP. Studies in a larger patient population are warranted to evaluate further the palliative effect of Re-188-HEDP.