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Nuklearmedizin 2016; 55(05): 188-195
DOI: 10.3413/Nukmed-0828-16-05
Original article
Schattauer GmbH

Treatment of painful bone metastases in prostate and breast cancer patients with the therapeutic radiopharmaceutical rhenium-188-HEDP

Clinical benefit in a real-world studyBehandlung schmerzender Knochenmetastasen bei Patienten mit Prostata- und Brustkrebs mit dem therapeutischen Radiopharmakon Rhenium-188-HEDPEine Studie zum klinischen Mehrwert in der täglichen Routine
Rogier Lange
1   Department of Clinical Pharmacy, Meander Medical Center, Amersfoort, The Netherlands
,
Floor Overbeek
1   Department of Clinical Pharmacy, Meander Medical Center, Amersfoort, The Netherlands
2   Department of Pharmaceutical Sciences, Utrecht University, The Netherlands
,
John M. H. de Klerk
3   Department of Nuclear Medicine, Meander Medical Center, Amersfoort, The Netherlands
,
Pieternel C. M. Pasker-de Jong
4   Department of Research, Meander Academy, Meander Medical Center, Amersfoort, The Netherlands
,
Alexandra M. van den Berk
3   Department of Nuclear Medicine, Meander Medical Center, Amersfoort, The Netherlands
,
Rob ter Heine
5   Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands
,
Cees J. Rodenburg
6   Department of Internal Medicine/Medical Oncology, Meander Medical Center, Amersfoort, The Netherlands
,
Anko Kooistra
7   Department of Urology, Meander Medical Center, Amersfoort, The Netherlands
,
N. Harry Hendrikse
8   Departments of Clinical Pharmacology & Pharmacy and Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands
,
Haiko J. Bloemendal
6   Department of Internal Medicine/Medical Oncology, Meander Medical Center, Amersfoort, The Netherlands
9   Department of Medical Oncology, University Medical Center, Utrecht, The Netherlands
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received: 12. Mai 2016

accepted in revised form: 11. Juli 2016

Publikationsdatum:
20. Dezember 2017 (online)

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Summary

Aim: Rhenium-188-HEDP (188Re-HEDP) is an effective radiopharmaceutical for the palliative treatment of osteoblastic bone metastases. However, only limited data on its routine use are available and its effect on quality of life (QoL) has not been studied. Therefore, we evaluated the clinical benefit of 188Re-HEDP in routine clinical care. Patients and methods: Prostate or breast cancer patients with painful bone metastases receiving 188Re-HEDP as a routine clinical procedure were eligible for evaluation. Clinical benefit was assessed in terms of efficacy and toxicity. Pain palliation and QoL were monitored using the visual analogue scale (VAS), corrected for opioid intake, and the EORTC QLQ-C30 Global health status/QoL-scale. Thrombocyte and leukocyte nadirs were used to assess haematological toxicity. Results: 45 and 47 patients were evaluable for pain palliation and QoL, respectively. After a single injection of 188Re-HEDP, the overall pain response rate was 69% and mean VAS-scores decreased relevantly and significantly (p < 0.05). Repeated treatment resulted in similar pain response. The overall QoL response rate was 68% and mean Global health status/QoL-scores increased relevantly and significantly. Haematological side effects were mild and transient. Conclusion: The clinically relevant response on pain and quality of life and the limited adverse events prove clinical benefit of treatment with 188Re-HEDP and support its use in routine clinical care. Its effectiveness appears comparable to that of external beam radiotherapy.

Zusammenfassung

Ziel: Rhenium-188-HEDP (188Re-HEDP) ist ein effektives Radiopharmakon für die palliative Behandlung von osteoblastischen Knochenmetastasen. Nur begrenzte Daten über die Routinebehandlung stehen zur Verfügung. Ihre Wirkung auf die Lebensqualität (QoL) wurde bisher nicht untersucht. Daher untersuchten wir den klinischen Mehrwert von 188Re-HEDP in der klinischen Standardbehandlung. Patienten und Methoden: Patienten mit ossär metastasierten Prostata-oder Brustkrebs, die 188Re-HEDP als Standardbehandlung erhalten haben, nahmen Teil an dieser Evaluation. Der klinische Mehrwert wurde auf die Effektivität und Toxizität untersucht. Die Schmerzlinderung wurde gemessen mit der Visuellen Analogskala (VAS), für Opioid-Einnahme korrigiert. Für die Auswertung von QoL wurde die EORTC QLQ-C30 Global health status/QoL-Skala verwendet. Die Thrombozyten und Leukozyten-Nadir wurden benutzt um die hämatologische Toxizität zu bewerten. Ergebnisse: Es wurden 45 Patienten für die Schmerzbehandlung beziehungsweise 47 Patienten für QoL ausgewertet. Nach einer einzigen Injektion betrug die gesamte Response-Rate auf Schmerzen 69% und die mittleren VAS-Werte sanken relevant und signifikant (p < 0,05). Die wiederholte Behandlung führte zu einer ähnlichen Schmerzreaktion. Die gesamte QoL-Ansprechrate war 68% und der mittlere Global health status/QoL-scores waren relevant und signifikant erhöht. Die hämatologischen Nebenwirkungen waren mild und vorübergehend. Schlussfolgerung: Die klinisch relevante Reaktion auf Schmerz und Lebensqualität und die begrenzte Toxizität beweisen den klinischen Mehrwert einer Behandlung mit 188Re-HEDP. Es unterstützt die Verwendung in der klinischen Standardbehandlung. Seine Effektivität scheint vergleichbar zu sein mit externer Strahlentherapie.

Keywords

Bone metastases - radionuclide therapy - rhenium- 188-HEDP - pain palliation - quality of life - haematological toxicity

Schlüsselwörter

Knochenmetastasen - Radionuklidtherapie - Rhenium-188-HEDP - Schmerzlinderung - Lebens qualität - hämatologische Toxizität
 

  • References

  • 1 Aaronson NK, Ahmedzai S, Bergman B. et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993; 85: 365-376.
    CrossrefPubMedGoogle Scholar
  • 2 Argyrou M, Valassi A, Andreou M. et al. Rhenium-188 production in hospitals, by W-188/Re-188 generator, for easy use in radionuclide therapy. Int J Mol Imaging 2013; 2013: 1-7.
    Google Scholar
  • 3 Autio KA, Pandit-Taskar N, Carrasquillo JA. et al. Repetitively dosed docetaxel and 153samarium-EDTMP as an antitumor strategy for metastatic castration-resistant prostate cancer. Cancer 2013; 119: 3186-3194.
    CrossrefPubMedGoogle Scholar
  • 4 Beiki D, Tajik M, Haddad P. et al. Effectiveness and complications of 188Re-HEDP in palliative treatment of diffuse skeletal metastases. Iran J Nucl Med 2014; 23: 44-48.
    Google Scholar
  • 5 Biersack H-J, Palmedo H, Andris A. et al. Palliation and survival after repeated 188Re-HEDP therapy of hormone-refractory bone metastases of prostate cancer: a retrospective analysis. J Nucl Med 2011; 52: 1721-1726.
    CrossrefPubMedGoogle Scholar
  • 6 Bodei L, Lam M, Chiesa C. et al. EANM procedure guideline for treatment of refractory metastatic bone pain. Eur J Nucl Med Mol Imaging 2008; 35: 1934-1940.
    CrossrefPubMedGoogle Scholar
  • 7 Cheng A, Chen S, Zhang Y. et al. The tolerance and therapeutic efficacy of Rhenium-188 hydroxyethylidene diphosphonate in advanced cancer patients with painful osseous metastases. Cancer Biother Radiopharm 2011; 26: 237-245.
    CrossrefPubMedGoogle Scholar
  • 8 Chow E, Wong R, Hruby G. et al. Prospective patient-based assessment of effectiveness of palliative radiotherapy for bone metastases. Radiother Oncol 2001; 61: 77-82.
    CrossrefPubMedGoogle Scholar
  • 9 Chow E, Zeng L, Salvo N. et al. Update on the systematic review of palliative radiotherapy trials for bone metastases. Clin Oncol 2012; 24: 112-124.
    CrossrefPubMedGoogle Scholar
  • 10 Cocks K, King MT, Velikova G. et al. Quality, interpretation and presentation of European Organisation for Research and Treatment of Cancer quality of life questionnaire core 30 data in randomised controlled trials. Eur J Cancer 2008; 44: 1793-1798.
    CrossrefPubMedGoogle Scholar
  • 11 Cramarossa G, Chow E, Zhang L. et al. Predictive factors for overall quality of life in patients with advanced cancer. Support Care Cancer 2013; 21: 1709-1716.
    CrossrefPubMedGoogle Scholar
  • 12 Farrar JT, Young JP, LaMoreaux L. et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001; 94: 149-158.
    CrossrefPubMedGoogle Scholar
  • 13 Fizazi K, Beuzeboc P, Lumbroso J. et al. Phase II trial of consolidation docetaxel and samarium-153 in patients with bone metastases from castration-resistant prostate cancer. J Clin Oncol 2009; 27: 2429-2435.
    CrossrefPubMedGoogle Scholar
  • 14 Groenvold M, Klee MC, Sprangers MAG. et al. Validation of the EORTC QLQ-C30 quality of life questionnaire through combined qualitative and quantitative assessment of patient-observer agreement. J Clin Epidemiol 1997; 50: 441-450.
    CrossrefPubMedGoogle Scholar
  • 15 Hoskin PJ. Bisphosphonates and radiation therapy for palliation of metastatic bone disease. Cancer Treat Rev 2003; 29: 321-327.
    CrossrefPubMedGoogle Scholar
  • 16 King MT. The interpretation of scores from the EORTC quality of life questionnaire QLQ-C30. Qual Life Res 1996; 5: 555-567.
    CrossrefPubMedGoogle Scholar
  • 17 Knapp FFJ, Beets AL, Guhlke S. et al. Availability of rhenium-188 from the alumina-based tungsten-188/rhenium-188 generator for preparation of rhenium-188-labeled radiopharmaceuticals for cancer treatment. Anticancer Res 1997; 17: 1783-1795.
    Google Scholar
  • 18 Kurosaka S, Satoh T, Chow E. et al. EORTC QLQ-BM22 and QLQ-C30 quality of life scores in patients with painful bone metastases of prostate cancer treated with strontium-89 radionuclide therapy. Ann Nucl Med 2012; 26: 485-491.
    CrossrefPubMedGoogle Scholar
  • 19 Li S, Liu J, Zhang H. et al. Rhenium-188 HEDP to treat painful bone metastases. Clin Nucl Med 2001; 26: 919-922.
    CrossrefPubMedGoogle Scholar
  • 20 Liepe K, Hliscs R, Kropp J. et al. Rhenium-188-HEDP in the palliative treatment of bone metastases. Cancer Biother Radiopharm 2000; 15: 261-265.
    CrossrefPubMedGoogle Scholar
  • 21 Liepe K, Kotzerke J. A comparative study of 188Re-HEDP, 186Re-HEDP, 153Sm-EDTMP and 89Sr in the treatment of painful skeletal metastases. Nucl Med Commun 2007; 28: 623-630.
    CrossrefPubMedGoogle Scholar
  • 22 Liepe K, Kotzerke J. Internal radiotherapy of painful bone metastases. Methods 2011; 55: 258-270.
    CrossrefPubMedGoogle Scholar
  • 23 Liepe K, Kropp J, Runge R. et al. Therapeutic efficiency of rhenium-188-HEDP in human prostate cancer skeletal metastases. Br J Cancer 2003; 89: 625-629.
    CrossrefPubMedGoogle Scholar
  • 24 Osoba D. Interpreting the meaningfulness of changes in health-related quality of life scores: lessons from studies in adults. Int J Cancer Suppl 1999; 12: 132-137.
    Google Scholar
  • 25 Palmedo H, Guhlke S, Bender H. et al. Dose escalation study with rhenium-188 hydroxyethylidene diphosphonate in prostate cancer patients with osseous metastases. Eur J Nucl Med 2000; 27: 123-130.
    CrossrefPubMedGoogle Scholar
  • 26 Palmedo H, Manka-Waluch A, Albers P. et al. Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: randomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidenediphosphonate. J Clin Oncol 2003; 21: 2869-2875.
    CrossrefPubMedGoogle Scholar
  • 27 Parker C, Nilsson S, Helle S. et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013; 369: 213-223.
    CrossrefPubMedGoogle Scholar
  • 28 Pillai MRA, Dash A, Knapp FF. Rhenium-188: availability from the 188W/188Re generator and status of current applications. Curr Radiopharm 2012; 5: 228-243.
    CrossrefPubMedGoogle Scholar
  • 29 Price DD, Mcgrath PA, Rafii A. et al. The validation of visual analogue scales as ratio scale measures for chronic and experimental pain. Pain 1983; 17: 45-56.
    CrossrefPubMedGoogle Scholar
  • 30 Roque I, Figuls M, Martinez-Zapata MJ, Scott-Brown M. et al. Radioisotopes for metastatic bone pain. Cochrane database Syst Rev 2011; 7: CD003347.
    Google Scholar
  • 31 Rubini G, Nicoletti A, Rubini D. et al. Radiometabolic treatment of bone-metastasizing cancer: from 186rhenium to 223radium. Cancer Biother Radiopharm 2014; 29: 1-11.
    CrossrefPubMedGoogle Scholar
  • 32 Soloway MS, Hardeman SW, Hickey D. et al. Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan. Cancer 1988; 61: 195-202.
    CrossrefPubMedGoogle Scholar
  • 33 Ter Heine R, Lange R, Breukels O. et al. Bench to bedside development of GMP grade rhenium-188-HEDP, a radiopharmaceutical for targeted treatment of painful bone metastases. Int J Pharm 2014; 465: 317-324.
    CrossrefPubMedGoogle Scholar
  • 34 Van der Linden YM, Lok JJ, Steenland E. et al. Single fraction radiotherapy is efficacious: a further analysis of the Dutch Bone Metastasis Study controlling for the influence of retreatment. Int J Radiat Oncol Biol Phys 2004; 59: 528-537.
    CrossrefPubMedGoogle Scholar
  • 35 Van Dodewaard-de Jong JM, de Klerk JMH, Bloemendal HJ. et al. A phase I study of combined docetaxel and repeated high activity 186Re-HEDP in castration-resistant prostate cancer (CRPC) metastatic to bone (the TAXIUM trial). Eur J Nucl Med Mol Imaging. 2011; 38: 1990-1998.
    CrossrefPubMedGoogle Scholar
  • 36 Van Dodewaard-de Jong JM, Oprea-Lager DE, Hooft L. et al. Radiopharmaceuticals for palliation of bone pain in patients with castration-resistant prostate cancer metastatic to bone: a systematic review. Eur Urol. 2015
    PubMedGoogle Scholar
  • 37 Von Elm E, Altman DG, Egger M. et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007; 370: 1453-1457.
    CrossrefPubMedGoogle Scholar
  • 38 Westhoff PG, de Graeff A, Monninkhof EM. et al. Quality of life in relation to pain response to radiation therapy for painful bone metastases. Int J Radiat Oncol 2015; 93: 694-701.
    CrossrefPubMedGoogle Scholar
  • 39 Zhang H, Tian M, Li S. et al. Rhenium-188-HEDP therapy for the palliation of pain due to osseous metastases in lung cancer patients. Cancer Biother Radiopharm 2003; 18: 719-726.
    CrossrefPubMedGoogle Scholar