Palliation and Survival After Repeated ¹⁸⁸Re-HEDP Therapy of Hormone-Refractory Bone Metastases of Prostate Cancer: A Retrospective Analysis

Abstract

This retrospective study compared the effects of single and multiple administrations of 186 Re-HEDP) on palliation and survival of prostate cancer patients presenting with more than 5 skeletal metastases. Methods: A total of 60 patients were divided into 3 groups. Group A (n 5 19) consisted of patients who had received a single injection; group B (n 5 19), patients who had 2 injections; and group C (n 5 22), patients who had 3 or more successive injections. The 188 Re-HEDP was prepared using non-carrieradded 188 Re obtained from an in-house 188 W/ 188 Re generator after dilution with carrier perrhenate. Patients' data available from the referring physicians-including prostate-specific antigen levels-were entered into a Windows-based matrix and analyzed using a statistical program. The Gleason scores were similar for all 3 groups. Results: Mean survival from the start of treatment was 4.50 6 0.81 mo (95% confidence interval [CI], 2.92-6.08) for group A, 9.98 6 2.21 mo (95% CI, 5.65-14.31) for group B, and 15.66 6 3.23 (95% CI, 9.33-22.0) for group C. Although the 3 groups did not differ in Gleason score, the number of lost life-years was significantly lower in group C than in groups A and B. Pain palliation was achieved in 89.5% of group A, 94.7% of group B, and 90.9% of group C. Conclusion: Posttreatment overall survival could be improved from 4.50 to 15.66 mo by multiple-injection bone-targeted therapy with 188 Re-HEDP, when compared with a single injection. Significant pain palliation was common and independent of administration frequency. Bone metastases are frequent and encountered by all physicians treating oncologic patients (1). About 50% of prostate cancer patients will develop bone metastases, which are predominantly osteoblastic. The osteolytic type has the tendency to develop fractures resulting in serious morbidity. Chronic pain syndrome is the most important complication of bone metastases and has a negative impact on quality of life. Many of these patients are candidates for radionuclide therapy, since as many as 50% of patients are reported to receive only inadequate pain treatment by alternative methods (2).Radionuclide therapy of bone metastases was first used decades ago by administration of 32 P (3), which is incorporated in the DNA of rapidly proliferating bone marrow cells as well as in the trabecular and cortical bone structures. A relatively low 1:2 ratio of normal bone to metastatic tissue has been estimated (4). More recently, a variety of b-emitting radioisotopes has been investigated for therapy of bone metastases. The maximal b-energy of these radioisotopes is in the range of 0.8-2.3 MeV, with an average b-energy between 0.27 and 0.8 MeV (Table 1). 89 Sr-chloride and ionic 90 Y are both calcium analogs that are sequestered as cations by bone in relation to the intensity of osseous metabolism (5-9). 89 Sr is excreted renally to 70%-90% and is eliminated from the vascular compartment within the first few hours (10). Except for bone uptake and excretion via the urinary system, there i...

Theranostics in nuclear medicine practice

“…Furthermore, patients with prostatic cancer have shown, after two [ 188 Re]Re-HEDP injections, a significantly higher response rate (92%), a prostate-specific antigen (PSA) decline >50% (38%), and a longer PFS (7 months) compared to patients who have had a single injection 52,53. Biersack et al showed an improved OS of 15.7 months in patients after repeated injections (≥3 injections) compared to patients with a single therapy 54. Besides transient bone marrow toxicity (thrombocytopenia grade III), the reported toxicity is low to moderate 51…”

Radionuclide Therapy of Bone Metastases

“…The mean survival increased from 7 to 13 months [42] in the double-dose cohort. A more recently published retrospective analysis of these data of the same group showed, in a total number of 60 patients suffering from bone metastases of hormone-refractory prostate cancer, an improvement of the mean survival from 4.5 to 15.66 months, in the subgroup with multiple (3 and more) successive administrations of 188 Re-HEDP [43]. Similar results were published by Turner and Claringbold [44] administering, in a phase II trial, either a single or repeated activity of 153 Sm-EDTMP.…”

Rhenium-188 Production in Hospitals, by W-188/Re-188 Generator, for Easy Use in Radionuclide Therapy

“…In another study by Palmedo et al [29] and Biersack [30], the analgesia and antitumor effects of repetitive administrations of Re-188 HEDP were evaluated in patients with metastatic prostate cancer, whereas minor toxicity problems were reported.…”