title: A phase IIa, nonrandomized study of radium-223 dichloride in advanced breast cancer patients with bone-dominant disease.
abstract: Radium-223 dichloride (radium-223) mimics calcium and emits high-energy, short-range alpha-particles resulting in an antitumor effect on bone metastases. This open-label, phase IIa nonrandomized study investigated safety and short-term efficacy of radium-223 in breast cancer patients with bone-dominant disease. Twenty-three advanced breast cancer patients with progressive bone-dominant disease, and no longer candidates for further endocrine therapy, were to receive radium-223 (50 kBq/kg IV) every 4 weeks for 4 cycles. The coprimary end points were change in urinary N-telopeptide of type 1 (uNTX-1) and serum bone alkaline phosphatase (bALP) after 16 weeks of treatment. Exploratory end points included sequential (18)F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) to assess metabolic changes in osteoblastic bone metastases. Safety data were collected for all patients. Radium-223 significantly reduced uNTX-1 and bALP from baseline to end of treatment. Median uNTX-1 change was -10.1 nmol bone collagen equivalents/mmol creatinine (-32.8 %; P = 0.0124); median bALP change was -16.7 ng/mL (-42.0 %; P = 0.0045). Twenty of twenty-three patients had FDG PET/CT identifying 155 hypermetabolic osteoblastic bone lesions at baseline: 50 lesions showed metabolic decrease (≥25 % reduction of maximum standardized uptake value from baseline) after 2 radium-223 injections [32.3 % metabolic response rate (mRR) at week 9], persisting after the treatment period (41.5 % mRR at week 17). Radium-223 was safe and well tolerated. Radium-223 targets areas of increased bone metabolism and shows biological activity in advanced breast cancer patients with bone-dominant disease.
authors.affiliation: Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield Cancer Research Centre, Sheffield, S10 2SJ, England, UK, r.e.coleman@sheffield.ac.uk.
authors.forename: Robert
authors.initials: R
authors.lastname: Coleman
authors.forename: Anne-Kirsti
authors.initials: AK
authors.lastname: Aksnes
authors.forename: Bjørn
authors.initials: B
authors.lastname: Naume
authors.forename: Camilo
authors.initials: C
authors.lastname: Garcia
authors.forename: Guy
authors.initials: G
authors.lastname: Jerusalem
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
authors.forename: Nancy
authors.initials: N
authors.lastname: Vobecky
authors.forename: Marcus
authors.initials: M
authors.lastname: Thuresson
authors.forename: Patrick
authors.initials: P
authors.lastname: Flamen
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D001859:Bone Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology* / Q000532:radiotherapy; D024042:Collagen Type I / Q000652:urine; D005260:Female; D006801:Humans; D008875:Middle Aged; D010455:Peptides / Q000652:urine; D011868:Radioisotopes / Q000627:therapeutic use; D011883:Radium / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D024042:Collagen Type I; D010455:Peptides; D011868:Radioisotopes; C052929:collagen type I trimeric cross-linked peptide; D000469:Alkaline Phosphatase; C581106:radium Ra 223 dichloride; D011883:Radium
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