Prospective Evaluation of Samarium-153-EDTMP Radionuclide Treatment for Bone Metastases in Patients with Hormone-Refractory Prostate Cancer

Abstract

Purpose: Bone is a common site of metastatic disease and the most frequent site of metastatic spread in patients with prostate cancer. Most patients with bone metastases complain of bone pains. This pain may be alleviated or eliminated by administration of radiotherapy at the site of metastases. Currently, two forms of radiotherapy administration exist: external-beam irradiation or intravenous administration of bone-seeking therapeutic radiopharmacon such as samarium-153-ethylene-diamino-tetramethylene-phosphonate (EDTMP). This radiopharmacon produces β-particles and concentrates in the areas of enhanced osteoblastic activity. The aim of this study was to assess the efficacy of ¹⁵³Sm-EDTMP therapy. Materials and Methods: 32 men (aged 50–83, mean 70 years) with bone disseminated hormone-refractory prostate cancer and bone pain received ¹⁵³Sm-EDTMP. Mean applied dosage was 40 MBq/kg of the patient’s body weight. Karnofsky performance status, pain score (numerical rating scale), analgesic score (WHO) and blood count were evaluated before, and 1 and 3 months after the treatment. Results: Significant pain relief was observed in 44 and 38% of patients, mild relief in 31 and 34% and no effect in 25 and 28% of patients, 1 and 3 months after administration, respectively. Pain palliation was accompanied by an improvement in mobility and a decrease in necessary dosage of analgesics. Mild and transient bone marrow suppression was observed as a side effect of ¹⁵³Sm-EDTMP treatment. None of the patients showed hematological toxicity grade 4, and only 2 showed grade 3 (NCI CTC). The majority of the patients had hematological toxicity grade 1 or 2. Conclusion: After ¹⁵³Sm-EDTMP administration, bone pain palliation was observed in 72% of patients for 3 months. Hematological toxicity after ¹⁵³Sm-EDTMP treatment was mild and transient.

Bone-targeting radiopharmaceuticals for the treatment of prostate cancer with bone metastases

“…Many dose-escalation studies have described the toxicity and efficacy of increasing doses of Sm-153 [38,73–76]. As with Sr-89, myelosuppression is the usual side-effect with dose-limiting thrombocytopenia seen in 20–42% of the patients [46].…”

Clinical Efficacy and Safety Comparison of 177Lu-EDTMP with 153Sm-EDTMP on an Equidose Basis in Patients with Painful Skeletal Metastases

“…The symptomatic treatment of skeletal pain due to metastases is complex and may require administration of drugs, including bisphosphonates and analgesics, and use of external-beam radiotherapy (5)(6)(7). Of the various options available, analgesics are the first step in the cascade.…”

“…Hormonal therapy and chemotherapy may be effective in alleviating the pain, but eventually the disease becomes refractory to these agents also (4). In limited metastatic disease, a short course of external-beam radiotherapy at a high dose per fraction effectively controls pain and has low toxicity, but toxicity rapidly increases as the field of irradiation increases (7,8).…”

“…In patients with multiple skeletal lesions and osteoblastic lesions on skeletal scintigraphy, systemic radiotherapy with radionuclides linked to a bone-seeking agent is an effective treatment option because of its efficacy, low cost, and comparatively low toxicity (7,9). Various radionuclides commercially available for systemic metabolic radiotherapy of bone pain include 32 P, 89 Sr, and 186 Re chelated with hydroxyethylidene diphosphonate and 153 Sm chelated with ethylene diamine tetramethylene phosphonate (EDTMP) (4,(10)(11)(12).…”

Pathobiology and management of prostate cancer-induced bone pain: recent insights and future treatments

“…P-32 is no longer used because of the associated myelosuppression (Lewington 1996). Sr-89 chloride (Metastron™) and Sm-153–lexidronam (Quadramet ® ) are effective for treating PCa cell-induced bone metastases (Liepe and Kotzerke 2007; Dolezal et al 2007), with 80 % of patients with prostate cancer-induced painful osteoblastic bony metastases achieving pain relief following strontium-89 administration (Robinson et al 1993). Concomitant administration of radiopharmaceuticals with bisphosphonates (Lam et al 2008) and chemotherapy (Amato et al 2008; Akerley et al 2002; Pagliaro et al 2003) improved patient survival and quality of life.…”