Phase 2 Study of a High Dose of 186Re-HEDP for Bone Pain Palliation in Patients with Widespread Skeletal Metastases

Abstract

186 Re-1-hydroxyethylidene-1,1-diphosphonate (HEDP) is an attractive radiopharmaceutical for the treatment of bone pain arising from skeletal metastatic lesions. Currently, 186 Re-HEDP is most commonly used in European countries. The aim of this study was to investigate the palliative efficacy and adverse effects of 186 Re-HEDP in patients with different types of cancers and skeletal bone pain. Methods: Nineteen (8 male, 11 female) patients with various cancers (breast, prostate, renal cell carcinoma, colon, and neuroendocrine tumors) and painful bone metastases were included in the study. A dose of 1,480-3,330 MBq (40-90 mCi) of 186 Re-HEDP was administered intravenously. The patients' level of pain relief was assessed by the Visual Analog Scale for 8 wk after treatment and by a weekly blood cell count to evaluate for hematologic toxicity. Results: The overall response rate was 89.5%, and the mean pain score assessed by the Visual Analog Scale was reduced from 9.1 to 5.3 after 1 wk (P 5 0.003). No adverse effects were reported by patients during intravenous administration or for up to 24 h after administration. A flare reaction was seen in 63.2% of patients, mainly during days 1-3, and lasted for 2-4 d. There was no significant correlation between the response to therapy and the flare reactions (P . 0.05). The nadir of platelet reduction occurred at the fourth or fifth week and led to platelet infusion in only 4 patients with a low baseline platelet count and diffuse skeletal metastases. Bone marrow suppression occurred in patients receiving higher doses, but no clinical problems were seen except in 2 patients who required packed cell transfusion similar to their prior transfusions. Conclusion: 186 Re-HEDP is an effective radiopharmaceutical for the palliative treatment of metastatic bone pain and has minimal adverse effects.Key Words: rhenium 186(tin) etidronate; pain palliation; bone metastasis Nucl Med Technol 2013; 41:192-196 DOI: 10.2967/jnmt.113.124297 The skeleton is the most common site of metastatic disease, and tumors arising from the breast, prostate, lung, thyroid, and kidney commonly spread to bone. The frequency of bone metastases has been estimated at 65%-75% in patients with breast and prostate cancer (1,2) and about 30%-40% in those with lung cancer (3). Bone pain, as the main symptom of skeletal metastases and the most common type of cancer-related pain, obviously has a negative impact on quality of life (4). Currently, the factors contributing to cancer pain are not completely understood (5,6), and metastatic bone pain might be poorly localized for external radiation therapy (7). Various modalities have been introduced for the treatment of bone metastases, including analgesics, hormone therapy, cytotoxic drugs, biphosphonates, and surgery; however, they are not effective in all patients with painful refractory skeletal metastases. An alternative approach is systemic administration of radiopharmaceuticals, which is a valuable and effective method for relieving bone pain in patients with ...

Palliative radiation therapy for bone metastases: Update of an ASTRO Evidence-Based Guideline

“…There has been an abundance of recently published studies, including clinical trials, affirming the safety and efficacy of familiar agents, samarium-153 and strontium-89, as well as rhenium-186 and radium-223 (Table 4). [17][18][19][20][21][22][23][24][25][26][27][28] Most intriguing is the growing evidence that, in patients with bone-only or bone-dominant disease, these agents may provide benefits beyond pain relief, including prevention of skeletal-related events and improved survival, although appropriate use of radiopharmaceuticals with the intention of improving survival is not addressed in this guideline. 18,29,30 Regarding the benefit of EBRT, a phase 3 RCT of samarium-153 with or without EBRT (8 Gy × 1 in 90% receiving EBRT) in metastatic prostate cancer with painful bony metastases demonstrated a significant improvement in pain relief with addition of EBRT and no extra toxicity.…”

Production and Clinical Applications of Radiopharmaceuticals and Medical Radioisotopes in Iran

“…Apart from its application in tumor imaging, Ga-67citrate remains a major tool for the detection of inflammation and infections. 30 67 Ga is locally produced in a medium-energy cyclotron, Cyclone 30, using 68 Zn(p,2n) 67 Ga followed by target dissolution and ion chromatography purification and formulation using citrate salt and is shipped to various nuclear medicine centers in the country for more than 20 years. 31 Local Clinical Evaluations.…”

“…It has a complex decay scheme, with electron capture, beta-emission, and positron emission branches, and it may be described as the archetypal "theranostic" radionuclide, producing excellent PET molecular imaging at low administered doses without major dosimetry or radiobiological concerns, and having potential for radionuclide therapy at high doses with radionuclide distribution and accurate dosimetry possible using PET imaging during therapy. 139 The most important production routes are via 64 Ni (p,n) and 68 Zn(p,αn) routes in small or medium-size cyclotrons or both. Owing to suitable half-life (12.7 hours), it can be used in the development of small size to large-size targeting molecules such as thiosemicarbazones, peptides, and also full size monoclonal antibodies.…”

“…The Re-186 HEDP is now available commercially in the country. 68 Re-188 HEDP 188 Re-HEDP is nonexpensive bone palliative radiopharmaceutical with favorable physical characteristics such as short half-life of 16.9 hours and maximal β energy of 2.1 MeV with a 15% γ-component of 155 keV. Re-188 is easily available from an in-house 188 W/ 188 Re generator.…”

Comparative efficacy, tolerability, and survival outcomes of various radiopharmaceuticals in castration-resistant prostate cancer with bone metastasis: a meta-analysis of randomized controlled trials

“…The acute toxicity of rhenium-186 was not reported in included trials; however, rhenium-186 is known to cause myelotoxicity as other β-emitting RPs. 26 Radium-223 was found to be the safest RP without any statistically significant hematological and nonhematological toxicity. However, late adverse events, especially the potential risk of second malignancies, which are of great concern, were not addressed in all included studies.…”