Dose escalation study with rhenium-188 hydroxyethylidene diphosphonate in prostate cancer patients with osseous metastases |
| |
| Authors: | Holger Palmedo Stefan Guhlke Hans Bender Johannes Sartor Georg Schoeneich Jörn Risse Frank Grünwald F.F. [Russ] Knapp Jr. Hans-Jürgen Biersack |
| |
| Affiliation: | (1) Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn, Germany, DE;(2) Department of Urology, University of Bonn, Germany, DE;(3) Nuclear Medicine Group, Oak Ridge National Laboratory, (ORNL), Oak Ridge, Tenn., USA, US |
| |
| Abstract: | 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 188Re-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 188Re-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 <200×109/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 188Re-HEDP is 3.3 GBq if the baseline thrombocyte count is below 200×109/l. In patients with thrombocyte counts significantly above 200×109/l, 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 188Re-HEDP. Studies in a larger patient population are warranted to evaluate further the palliative effect of 188Re-HEDP. Received 7 July and in revised form 6 October 1999 |
| |
| Keywords: | : Prostate cancer – Painful bone metastases – Rhenium-188 hydroxyethylidene diphosphonate – Haematotoxicity – Dose escalation |
| 本文献已被 SpringerLink 等数据库收录！ |
|
