A phase I study of samarium-153 ethylenediaminetetramethylene phosphonate therapy for disseminated skeletal metastases.
Thirty-five patients with disseminated skeletal metastases from a variety of tumor types underwent clinical trial of samarium-153 ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) on a day-patient basis. Individual beta radiation dosimetry was based on pharmacokinetic studies of a 20 mCi tracer dose of 153Sm-EDTMP. The retained skeletal activity varied unpredictably from 40% to 95% of the administered dose, but in all patients greater than 98% of the nonosseous activity was cleared in the urine within 6 hours. Prospective calculation of radiation dosimetry in each patient permitted an accurate dosage schedule based upon total red marrow exposure, starting at 100 cGy and escalating to 280 cGy to define the dose-limiting myelotoxicity. Pain was relieved in 22 of 34 evaluable patients (65%) for periods ranging from 4 to 35 weeks, following a single administration of 153Sm-EDTMP. Recurrence of pain responded to retreatment with 153Sm-EDTMP in five of nine patients. The dose-limiting toxicity was myelosuppression manifested particularly by delayed thrombocytopenia. Platelet counts less than 100 x 10(9)/L occurred in 42% of courses when bone marrow radiation absorbed dose exceeded 200 cGy. Myelosuppression was transient and platelet counts had recovered to pretreatment levels within 10 weeks of treatment. 153Sm-EDTMP is effective for the amelioration of pain due to disseminated skeletal metastases particularly with carcinoma of breast or prostate where 83% of patients experienced pain relief. In 15 of the 34 evaluable patients there was evidence of stabilization or regression of skeletal metastases on radiographs and follow-up technetium-99m methylene diphosphonate (99mTc-MDP) bone scans.
Turner
J H
JH
Department of Nuclear Medicine, Fremantle Hospital, Western Australia, NSW.
Claringbold
P G
PG
Hetherington
E L
EL
Sorby
P
P
Martindale
A A
AA
D001859:Bone Neoplasms / Q000532:radiotherapy / Q000556:secondary*; D004307:Dose-Response Relationship, Radiation; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010146:Pain / Q000532:radiotherapy; D011868:Radioisotopes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D012493:Samarium / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D011868:Radioisotopes; D012493:Samarium; C061972:samarium Sm-153 lexidronam