Evaluation of Efficacy and Toxicity of Treatment Using Rhenium-186 HEDP in Metastatic Bone Disease

Ziada, G.; Faris, L; Yacoub, Shreif; Elgazzar, Abdelhamid H.

doi:10.1159/000026092

Cited by 4 publications

(7 citation statements)

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“…This finding could explain why a better response is seen in patients who have received higher doses (19)(20)(21). On the other hand, it might be a reasonable justification for a good response in patients with few metastatic lesions treated with a lower administered activity (22)(23)(24).…”

Section: Discussionmentioning

confidence: 95%

“…bone markers, hemoglobin level, and previous treatments (14,23,24,36), but highly controversial issues remain. Although several studies have demonstrated that earlier treatment in patients in better clinical condition may improve the response rate (22)(23)(24), unfortunately radionuclide therapy is underutilized in Iran. This underutilization could be a result of limited referrals due to specialists' inadequate knowledge and misconceptions about adverse effects or to the restricted availability and expense of bone painpalliating radionuclides.…”

Section: Discussionmentioning

confidence: 99%

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

Pirayesh

Amoui

Mirzaee

et al. 2013

Journal of Nuclear Medicine Technology

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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 ...

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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

Pirayesh

Amoui

Mirzaee

et al. 2013

Journal of Nuclear Medicine Technology

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“…On the other hand, lower doses may be enough to get a good response in patients with few metastatic lesions. [ 11 18 19 31 ]…”

Section: Discussionmentioning

confidence: 99%

“…Possible side effects of this therapy can be significantly minimized upon careful selection of patients and administered dose. Although several studies have demonstrated that administering therapy, when the patient is in better clinical condition, may significantly improve the response rate,[ 18 19 31 ] this understanding has not been translated into a clinical practice to unleash the full potential of radionuclide therapy. This underutilization could be due to specialists' inadequate knowledge and misconceptions about the adverse effects of this mode of therapy or due to restricted availability and cost of bone pain-palliating radionuclides.…”

Section: Discussionmentioning

confidence: 99%

“…Another effective approach for relieving bone pain in patients with multifocal skeletal metastases is the systemic administration of radiopharmaceuticals. [ 4 8 9 10 11 12 13 ] Various bone-seeking beta-emitting radiopharmaceuticals such as 32 P as sodium orthophosphate,[ 14 ] 89 Sr-chloride,[ 15 16 17 18 19 20 21 22 ] 153 Sm-ethylenediamine tetramethylenephosphonic acid (EDTMP),[ 17 23 24 25 26 27 28 29 ] 186 Re-HEDP,[ 19 22 29 30 31 32 33 34 35 36 37 38 ] and 188 Re-HEDP have been clinically evaluated earlier. [ 29 39 40 41 42 43 44 45 46 47 48 ] 177 Lu-EDTMP is another bone pain-palliating agent which has established its clinically utility.…”

Section: Introductionmentioning

confidence: 99%

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Clinical utility of 188Rhenium-hydroxyethylidene-1,1-diphosphonate as a bone pain palliative in multiple malignancies

et al. 2018

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188Rhenium-hydroxyethylidene-1,1-diphosphonate (188Re-HEDP) is a clinically established radiopharmaceutical for bone pain palliation of patients with metastatic bone cancer. Herein, the effectiveness of 188Re-HEDP for the palliation of painful bone metastases was investigated in an uncontrolled initial trial in 48 patients with different types of advanced cancers. A group of 48 patients with painful bone metastases of lung, prostate, breast, renal, and bladder cancer was treated with 2.96–4.44 GBq of 188Re-HEDP. The overall response rate in this group of patients was 89.5%, and their mean visual analog scale score showed a reduction from 9.1 to 5.3 (P < 0.003) after 1 week posttherapy. The patients did not report serious adverse effects either during intravenous administration or within 24 h postadministration of 188Re-HEDP. Flare reaction was observed in 54.2% of patients between day 1 and day 3. There was no correlation between flare reaction and response to therapy (P < 0.05). Although bone marrow suppression was observed in patients receiving higher doses of 188Re-HEDP, it did not result in any significant clinical problems. The present study confirmed the clinical utility and cost-effectiveness of 188Re-HEDP for palliation of painful bone metastases from various types of cancer in developing countries.

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Phase I/II trials of 186Re-HEDP in metastatic castration-resistant prostate cancer: post-hoc analysis of the impact of administered activity and dosimetry on survival

Bacelar

Chittenden

Dearnaley

et al. 2016

Eur J Nucl Med Mol Imaging

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PurposeTo investigate the role of patient-specific dosimetry as a predictive marker of survival and as a potential tool for individualised molecular radiotherapy treatment planning of bone metastases from castration-resistant prostate cancer, and to assess whether higher administered levels of activity are associated with a survival benefit.MethodsClinical data from 57 patients who received 2.5–5.1 GBq of 186Re-HEDP as part of NIH-funded phase I/II clinical trials were analysed. Whole-body and SPECT-based absorbed doses to the whole body and bone lesions were calculated for 22 patients receiving 5 GBq. The patient mean absorbed dose was defined as the mean of all bone lesion-absorbed doses in any given patient. Kaplan–Meier curves, log-rank tests, Cox’s proportional hazards model and Pearson’s correlation coefficients were used for overall survival (OS) and correlation analyses.ResultsA statistically significantly longer OS was associated with administered activities above 3.5 GBq in the 57 patients (20.1 vs 7.1 months, hazard ratio: 0.39, 95 % CI: 0.10–0.58, P = 0.002). A total of 379 bone lesions were identified in 22 patients. The mean of the patient mean absorbed dose was 19 (±6) Gy and the mean of the whole-body absorbed dose was 0.33 (±0.11) Gy for the 22 patients. The patient mean absorbed dose (r = 0.65, P = 0.001) and the whole-body absorbed dose (r = 0.63, P = 0.002) showed a positive correlation with disease volume. Significant differences in OS were observed for the univariate group analyses according to disease volume as measured from SPECT imaging of 186Re-HEDP (P = 0.03) and patient mean absorbed dose (P = 0.01), whilst only the disease volume remained significant in a multivariable analysis (P = 0.004).ConclusionThis study demonstrated that higher administered activities led to prolonged survival and that for a fixed administered activity, the whole-body and patient mean absorbed doses correlated with the extent of disease, which, in turn, correlated with survival. This study shows the importance of patient stratification to establish absorbed dose–response correlations and indicates the potential to individualise treatment of bone metastases with radiopharmaceuticals according to patient-specific imaging and dosimetry.

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Evaluation of Efficacy and Toxicity of Treatment Using Rhenium-186 HEDP in Metastatic Bone Disease

Cited by 4 publications

References 10 publications

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

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

Clinical utility of 188Rhenium-hydroxyethylidene-1,1-diphosphonate as a bone pain palliative in multiple malignancies

Phase I/II trials of 186Re-HEDP in metastatic castration-resistant prostate cancer: post-hoc analysis of the impact of administered activity and dosimetry on survival

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