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

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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 15 Hoskin PJ. Bisphosphonates and radiation therapy for palliation of metastatic bone disease. Cancer Treat Rev 2003; 29: 321-327.
• 16 King MT. The interpretation of scores from the EORTC quality of life questionnaire QLQ-C30. Qual Life Res 1996; 5: 555-567.
• 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.
• 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.
• 19 Li S, Liu J, Zhang H. et al. Rhenium-188 HEDP to treat painful bone metastases. Clin Nucl Med 2001; 26: 919-922.
• 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.
• 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.
• 22 Liepe K, Kotzerke J. Internal radiotherapy of painful bone metastases. Methods 2011; 55: 258-270.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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
• 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.
• 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.
• 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.