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Management Of Metastatic Bone Pain With Repeated Doses Of 186Re-HEDP In Patients Under Therapy With Zoledronic Acid: Safe And Additively Effective

November 21, 2019

UroToday - Treatment with 186 Rhenium-l,l-hydroxyethylidene diphosphonate (186Re-HEDP) has long been proven safe for palliation of bone pain in patients with widespread osseous metastases. On the basis that, systematic studies evaluating the effect of 186Re-HEDP combined with biphosphonates, especially when concerning repeated doses of the radiopharmaceutical are scarce. The present study focused on the comparison of pain response and haematological toxicity between single and multiple treatments with 186Re-HEDP, in the same group of patients, during a time period with no evidence of extraosseous disease progression.

Eligible patients should be on a stable regimen of zoledronic acid therapy. Patients, who had been administered chemotherapy or radiotherapy, had hormonal treatment alterations, developed visceral metastases or rapidly progressive metastatic disease were excluded from analysis. Thus for in-study patients, the possibility of development of extraosseous painful sites during the study period and also of any palliative or toxical effects of synergic therapies other than the combination of 186Re-HEDP and zoledronic acid was diminished. Furthermore, there was no need for a group of controls, since each patient served as a control of him/herself as regards pain palliation and haematological toxicity throughout the protocol period.

The post-therapy response after 186Re-HEDP treatment in the current study ranged from 78.9% to 83.3% (overall 80.6%), without significant percentile differences among various response levels between single-dose and multi-dose therapies, meaning that the percentage of patients with a significant improvement in pain indices was not related to the total number of therapeutic doses administered. Yet, the duration of the palliative effect was highly variable; the mean time to onset of response, mean duration of response, or time to maximum pain relief could not be estimated accurately because of inherent methodological problems in time-points definition. Nevertheless, in the present study, two thirds of the patients had pain response duration longer than 3 months, with no trend for longer response, between single and multiple therapies and also with no difference between males and females.

Myelotoxicity is generally cumulative in patients receiving repeated radionuclide therapies for recurrent symptoms, but the toxicity of repeated treatment is not easily distinguished from the effects of underlying tumour progression. In our case, the overall profile of haematological toxicity observed after administration of the standard dose of 186Re-HEDP was consistent with the general experience regarding the use of this radiopharmaceutical for bone pain palliation purposes. Half of the patients in the current study (6/12) presented with grade I anaemia either before the first dose of 186Re-HEDP, or after the second or third one, but none presented with leuco/thrombocytopenia; a slight percentile increase in all respective toxicity figures was albeit observed after each treatment without cases of severe post-therapeutic haematological toxicity (grade IIIā€"IV anaemia, leucocytopenia or thrombocytopenia, according to WHO criteria). With respect to baseline Hgb, WBC or PLT blood counts, only thrombocytes showed a tendency for greater decrease after repeated treatments (P = 0.024). Thus, repeated administration is also safe; there is no limit to the total administered activity provided that baseline blood counts are not very low and are not declining rapidly, and the time interval from previous 186Re-HEDP treatments is sufficient to have permitted the recovery of bone marrow.

As a result, this retrospective study has proved that multiple schemes of 186Re-HEDP treatment are additively both effective and safe compared to one scheme of this radiopharmaceutical, in a selected group of breast or prostate cancer patients with painful bone metastases. Hence, repeated combined protocols of 186Re-HEDP and zoledronic acid show promising clinical results with minimal side-effects.

Athanasios Zafeirakis, MD, PhD as part of Beyond the Abstract on UroToday. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations, etc., of their research by referencing the published abstract.

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