This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nilsson, S. Articles by Bruland, O. S. Search for Related Content PubMed PubMed Citation Articles by Nilsson, S. Articles by Bruland, O. S.

First Clinical Experience with -Emitting Radium-223 in the Treatment of Skeletal Metastases

Authors' Affiliations: ¹ Radiumhemmet, The Karolinska Hospital and Institute, Stockholm, Sweden; ² Algeta ASA, ³ Department Group of Clinical Medicine, University of Oslo, Department of Oncology, The Norwegian Radium Hospital, Oslo, Norway; ⁴ The University Hospital of Tromsø, Tromsø, Norway; and ⁵ Mälarsjukhuset, Eskilstuna, Sweden

Requests for reprints: Roy H. Larsen, Algeta ASA, P.O. Box 54, N-0411 Oslo, Norway. Phone: 47-2300-7990; Fax: 47-2300-7991; E-mail: roy.larsen{at}algeta.com.

Purpose: The main goals were to study the safety and tolerability of the -emitter radium-223 (²²³Ra) in breast and prostate cancer patients with skeletal metastases. In addition, pain palliation was evaluated.

Experimental Design: Fifteen prostate and 10 breast cancer patients enrolled in a phase I trial received a single i.v. injection of ²²³Ra. Five patients were included at each of the dosages: 46, 93, 163, 213, or 250 kBq/kg and followed for 8 weeks. Palliative response was evaluated according to the pain scale of the European Organization for Research and Treatment of Cancer QLQ C30 questionnaire at baseline and at 1, 4, and 8 weeks after injection.

Results: Weekly blood sampling during follow-up revealed mild and reversible myelosuppression with nadir 2 to 4 weeks after the injection. Importantly, for thrombocytes only grade 1 toxicity was reported. Grade 3 neutropenia and leucopenia occurred in two and three patients, respectively. Mild, transient diarrhea was observed in 10 of the 25 patients. Nausea and vomiting was more frequently observed in the highest dosage group. Serum alkaline phosphatase decreased with nadir averages of 29.5% in females and 52.1% in males. Pain relief was reported by 52%, 60%, and 56% of the patients after 7 days, 4, and 8 weeks, respectively. ²²³Ra cleared rapidly from blood and was below 1% of initial level at 24 hours. Gamma camera images indicated, in accordance with pretreatment ^99mTc-MDP scans, accumulation of ²²³Ra in skeletal lesions. Elimination was mainly intestinal. Median survival exceeded 20 months.

Conclusions: ²²³Ra was well tolerated at therapeutically relevant dosages. Phase II studies have therefore been initiated.

Key Words: -Particle Therapy • Metabolic Targeting • Phase I clinical trial

This article has been cited by other articles:

				M M Muresan, P Olivier, J Leclere, F Sirveaux, L Brunaud, M Klein, R Zarnegar, and G Weryha Bone metastases from differentiated thyroid carcinoma Endocr. Relat. Cancer, March 1, 2008; 15(1): 37 - 49. [Abstract] [Full Text] [PDF]

				M. R. Zalutsky, D. A. Reardon, G. Akabani, R. E. Coleman, A. H. Friedman, H. S. Friedman, R. E. McLendon, T. Z. Wong, and D. D. Bigner Clinical Experience with {alpha}-Particle Emitting 211At: Treatment of Recurrent Brain Tumor Patients with 211At-Labeled Chimeric Antitenascin Monoclonal Antibody 81C6 J. Nucl. Med., January 1, 2008; 49(1): 30 - 38. [Abstract] [Full Text] [PDF]

				J. Dahle, J. Borrebaek, T. J. Jonasdottir, A. K. Hjelmerud, K. B. Melhus, O. S. Bruland, O. W. Press, and R. H. Larsen Targeted cancer therapy with a novel low-dose rate {alpha}-emitting radioimmunoconjugate Blood, September 15, 2007; 110(6): 2049 - 2056. [Abstract] [Full Text] [PDF]

				A. Lipton, J. R. Berenson, J.-J. Body, B. F. Boyce, O. S. Bruland, M. A. Carducci, C. S. Cleeland, D. R. Clohisy, R. E. Coleman, R. J. Cook, et al. Proceedings of the 1st Cambridge Conference on Advances in Treating Metastatic Bone Cancer, October 28-29, 2005, Cambridge, Massachusetts, USA. Clin. Cancer Res., October 15, 2006; 12(20 Pt 2): 6209s - 6319s. [Abstract] [Full Text] [PDF]

				O. S. Bruland, S. Nilsson, D. R. Fisher, and R. H. Larsen High-Linear Energy Transfer Irradiation Targeted to Skeletal Metastases by the {alpha}-Emitter 223Ra: Adjuvant or Alternative to Conventional Modalities? Clin. Cancer Res., October 15, 2006; 12(20): 6250s - 6257s. [Abstract] [Full Text] [PDF]