title: Dose escalation study with rhenium-188 hydroxyethylidene diphosphonate in prostate cancer patients with osseous metastases.
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 <200x10(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 188Re-HEDP is 3.3 GBq if the baseline thrombocyte count is below 200x10(9)/l. In patients with thrombocyte counts significantly above 200x10(9)/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.
authors.affiliation: Department of Nuclear Medicine, University of Bonn, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Palmedo
authors.forename: S
authors.initials: S
authors.lastname: Guhlke
authors.forename: H
authors.initials: H
authors.lastname: Bender
authors.forename: J
authors.initials: J
authors.lastname: Sartor
authors.forename: G
authors.initials: G
authors.lastname: Schoeneich
authors.forename: J
authors.initials: J
authors.lastname: Risse
authors.forename: F
authors.initials: F
authors.lastname: Grünwald
authors.forename: F F
authors.initials: FF
authors.lastname: Knapp
authors.forename: H J
authors.initials: HJ
authors.lastname: Biersack
mesh_terms: D001859:Bone Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D004307:Dose-Response Relationship, Radiation; D012968:Etidronic Acid / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010147:Pain Measurement; D010148:Intractable Pain / Q000532:radiotherapy; D010166:Palliative Care; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D011868:Radioisotopes / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D012211:Rhenium / Q000627:therapeutic use*
chemical_list: D011868:Radioisotopes; D012211:Rhenium; D012968:Etidronic Acid