153Sm-EDTM for bone pain treatment in skeletal metastases

Abstract

Metastases to the skeleton occur in approximately 75% of patients with advanced breast carcinoma, and skeletal metastases are present in >90 % of patients who die from breast carcinoma (Coleman and Rubens 1987; Hortobagyi 1991). Bone disease is most often lytic or mixed lytic/blastic, determining a series of disease-related events that have the most significant impact on quality of life in these relatively long-surviving patients (Kakonen and Mundy 2003). The symptomatic treatment of skeletal pain due to metastases from breast cancer is a complex task that may require administration of drugs, including bisphosphonates and analgesics, and external beam radiotherapy (Lipton 2000; Hoskin 2003). Bisphosphonates target osteoclast-mediated bone resorption and reduce the skeletal complication rate arising from osteolytic metastases in breast cancer (Coleman 2000). External beam radiotherapy allows an effective pain control with a relatively low dose and a low toxicity if the metastatic disease is not extensive, but the toxicity rapidly increases with wide irradiation fields (Hoskin 1995). Systemic radioisotope therapy with radionuclides linked to a bone seeker agent may be the option of choice for the radiation treatment of patients with multiple skeletal localizations due to its efficacy, low cost and low toxicity (Dearnaley et al. 1992). Nonetheless, it still appears to have a low priority among medical oncologists and remain underutilized. Physician education regarding radioisotope therapy should be improved, and clinical trials to evaluate newer treatment paradigms including radionuclides should be strongly encouraged (Damerla et al. 2005). Radionuclides suitable for systemic metabolic radiotherapy of bone pain, and commercially available, include 89Sr, 186Re chelated by HEDP and 153Sm chelated by EDTMP (Serafini 1994; McEwan 1997; Serafini 2001). The main physical characteristic of the three radionuclides are illustrated in Table 21.1. Beta emitters with short half-lives, such as 186Re and 153Sm, deliver their radiation dose at higher dose rates, which may be more therapeutically effective than equivalent doses given at lower dose rates. The short range of 153Sm beta emission, actually the shortest of the three available radionuclides, may be of advantage limiting red marrow irradiation (Serafini 2000, 2001). 153Sm-EDTMP was developed by Goeckeler at the University of Missouri as a 1:1 chelation complex of radioactive 153Sm and a tetraphosphonate, (ethylenediamine- tetramethylene phosphonate), also known as lexidronam (Goeckeler et al. 1987). 153Sm-EDTMP shows high selective skeletal uptake like conventional 99mTc bone scanning agents: its bone localization is by chemiabsorption of the tetraphosphate by hydroxyapatite and by the formation of samarium oxide involving oxygen of the hydroxyapatite. The therapeutic effect is due to the irradiation by the short range beta emission of 153Sm. Early phase I/II studies were published over 10 years ago (Turner et al. 1989; Podoloff et al. 1991; Eary et al. 1993; Turner and Claringbold 1991), and since then this agent has been clinically used for pain palliation in symptomatic bone metastases from several cancers, mainly prostate and breast carcinoma. This review will address the characteristics of 153Sm-EDTMP as a radiopharmaceutical and its clinical applications for bone pain palliation in breast carcinoma. © 2008 Springer-Verlag Berlin Heidelberg.