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Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer

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Abstract

Rhenium-186 hydroxyethylidene diphosphonate (186Re-HEDP) has been used for the palliative treatment of metastatic bone pain. A phase 1 dose escalation study was performed using 186Re-HEDP Twenty-four patients with hormone-resistant prostate cancer entered the study. Each patient had at least four bone metastases and adequate haematological function. Groups of at least three consecutive patients were treated with doses starting at 1295 MBq and increasing to 3515 MBq (escalated in increments of 555 MBq). Thrombocytopenia proved to be the dose-limiting toxicity, while leucopenia played a minor role. Early death occurred in one patient (10 days after administration) without clear relationship to the 186Re-HEDP therapy. Transient neurological dysfunction was seen in two cases. Two patients who received 3515 MBq 186Re-HEDP showed grade 3 toxicity (thrombocytes 25–50 × 109/1), defined as unacceptable toxicity. After treatment alkaline phosphatase levels showed a transient decrease in all patients (mean: 26% ± 10% IUA; range: 11%–44%). Prostate-specific antigen values showed a decline in eight patients, preceded by a temporary increase in three patients. From this study we conclude that the maximally tolerated dose of 186Re-HEDP is 2960 MBq. A placebo-controlled comparative study on the efficacy of 186Re-HEDP has been initiated.

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Authors and Affiliations

  1. Department of Nuclear Medicine, University Hospital Utrecht, Heidelberglaan 100, NL-3584, CX Utrecht, The Netherlands

    John M. H. de Klerk, Alfred D. van het Schip, Shiuw H. Han, Jacques M. S. R. Quirijnen & Peter R van Rijk

  2. Oncology Section, Department of Internal Medicine, University Hospital Utrecht, Heidelberglaan 100, NL-3584, CX Utrecht, The Netherlands

    Bernard A. Zonnenberg & Geert H. Blijham

  3. Center for Hospital Pharmacy, University Hospital Utrecht, Heidelberglaan 100, NL-3584, CX Utrecht, The Netherlands

    Aalt van Dijk

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  1. John M. H. de Klerk
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  2. Bernard A. Zonnenberg
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  3. Alfred D. van het Schip
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  8. Peter R van Rijk
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de Klerk, J.M.H., Zonnenberg, B.A., van het Schip, A.D. et al. Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer. Eur J Nucl Med 21, 1114–1120 (1994). https://doi.org/10.1007/BF00181067

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  • DOI: https://doi.org/10.1007/BF00181067

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