Samarium ? 153 EDTMP therapy of disseminated skeletal metastasis

Abstract

153Sm-EDTMP (ethylenediaminetetramethylene phosphonate), prepared from a kit, was administered to 28 patients in a clinical trial of therapy for painful skeletal metastases unresponsive to all conventional treatment. The 103 keV gamma emission of 153Sm was utilized for prospective individual estimation of beta radiation absorbed dose to red marrow to minimize myelotoxicity and provide optimum internal radiotherapy to skeletal metastases in each patient. Pain relief occurred within 14 days of administration of 153Sm-EDTMP in 15 of 19 patients (79%) who could be evaluated at 6 weeks, when clinical response was maximal. Duration of response ranged from 4 to 35 weeks. Recurrence of pain responded to retreatment with 153Sm-EDTMP in five of eight cases. No dose-response relationship was apparent for pain relief but reversible myelotoxicity was frequently observed at radiation absorbed doses to bone marrow greater than or equal to 270 cGy. Dosimetry calculation was based on pharmacokinetic studies of a tracer administration of 153Sm-EDTMP in each patient. Assumptions inherent in this prospective method of predicting dose to bone marrow were validated experimentally. Biodistribution studies in rats demonstrated rapid skeletal uptake and long term retention of 153Sm-EDTMP in bone over 5 days. Urinary clearance accounted for 40% of injected dose, and less than 1.0% of administered activity was retained in non osseous tissue. Microdensitometry of autoradiographs of sheep vertebra and femur confirmed surface uptake of 153Sm-EDTMP in cortical bone and demonstrated relatively high trabecular bone activity which is the major component of radiation absorbed dose to bone marrow. Haematological studies in rabbits showed 153Sm-EDTMP-induced myelotoxicity to be transient and no histopathological abnormalities were demonstrable with doses ten times greater than those administered to patients.

Samarium-153 ethylenediamine tetramethylene phosphonate therapy for bone pain palliation in skeletal metastases

“…This was comparable to the rates reported by the controlled clinical trials [12][13][14] and the other uncontrolled studies reported in literature, [17][18][19] where response rates varied from 61 to 95%. The dose of Sm-153 used in these studies ranged from 18.5 to 111 MBq/kg.…”

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

“…We dosed 177 Lu-EDTMP at 37 MBq/kg of body weight to be comparable to the dose of 153 Sm-EDTMP. With 153 Sm-EDTMP, pain was relieved in 75% of patients overall, which is comparable to the 61%-95% reported for controlled clinical trials and other uncontrolled studies (24)(25)(26)(27)(28)(29).…”

Gemcitabine Radiosensitization after High-Dose Samarium for Osteoblastic Osteosarcoma

“…Gemcitabine schedule was initially repetitive daily dosing with daily  2, day of rest, then daily  2 (patient 1; patient choice not to get dose 3 of 5), then daily  5 (patient 2). When this patient developed unexpected grade 4 mucositis, the schedule the single dose schedule 18 to 24 hours after was used (patients [3][4][5][6][7][8][9][10][11][12][13][14].…”