Samarium is now being used along with Strontium. Samarium has a short half-life (46 hours) with 75% of the dose absorbed within 4 days. The beta particle energy (233keV) penetrates 1.7mm in bone and 3.1 mm in soft tissue. There is some myelosupression with wbc and platelets nadir of 40-50% baseline within 3-5 wk. and return to baseline by 8wks. The usual dose is 1mCi/kg and the patient should be hydrates (500ml prior to administration) and have CBC's checked weekly for about 8 wk. In trials, 48-54% get pain relief.(see Quadramet for more information.) and the studies below. It is quite expensive (~ $2300 a dose) but is usually covered by insurance.

Drugs Aging 1997 Nov;11(5):413-8; discussion 419

Samarium 153Sm lexidronam.

Lamb. Samarium 153Sm lexidronam is a medium energy beta-emitting radioisotope chelated to the tetraphosphate, ethylenediaminetetramethylenephosphonic acid (EDTMP). 153Sm has a physical half-life of 1.9 days. Samarium 153Sm lexidronam concentrates in bone tissue and has a metastatic lesion: normal bone ratio of 4. Clearance of nonskeletal radioactivity after administration of samarium 153Sm lexidronam is rapid, and is almost complete from the blood and urine within 1 and 6 hours, respectively. Some degree of pain relief was achieved in 72% of patients with bone metastases after a single dose of samarium 153Sm lexidronam 1 mCi/kg (37 MBq/kg) compared with 44% of placebo recipients (p < 0.025). Relief was generally attained within 2 weeks and lasted for a median of 8 to 15 weeks. After recurrence of pain, a second dose of samarium 153Sm lexidronam may produce further pain relief in some patients. The dose-limiting toxicity of samarium 153Sm lexidronam is reversible myelosuppression.

Eur J Cancer 1997 Sep;33(10):1583-91

A dose-controlled study of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) in the treatment of patients with painful bone metastases.

Resche One hundred and fourteen patients with painful bone metastases participated in this randomised, dose-controlled study of the efficacy and safety of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP), a systemically administered radiopharmaceutical. Among subsets of patients examined, female patients with breast cancer receiving 1.0 mCi/kg had the most noticeable improvement. The physicians judged that approximately half of the patients in each dose group were experiencing some degree of pain relief by week 2. This value increased to 55% for the 0.5 mCi/kg group and 70% for the 1.0 mCi/kg group at week 4. More patients in the higher dose group (54%) than in the lower dose group (44%) completed the 16-week study. A predictable level of dose-related marrow suppression was the only toxicity associated with 153Sm-EDTMP treatment. Values for platelets and WBCs reached nadirs at 3 or 4 weeks with both doses and recovered by 8 weeks. Even at their lowest point, the values were generally higher than those associated with infectious or haemorrhagic complications. Myelotoxicity was no greater in female patients than in male patients. Long-term follow-up revealed longer survival among breast cancer patients who had received the higher dose than among those who had received the lower dose. The results suggest that the 1.0 mCi/kg dose of 153Sm-EDTMP is safe and effective for the treatment of painful bone metastases.

Radiother Oncol 1997 May;43(2):175-9

Dose response relationship and multiple dose efficacy and toxicity of samarium-153-EDTMP in metastatic cancer to bone.

Alberts Multiple doses were given to patients on the 0.75 mCi/kg and 1.5 mCi/kg dose levels. RESULTS: At all dose levels adequate pain control was achieved in 78-95% of patients. The duration of pain control was 40-56 days with the best results in the 1.5 mCi/kg group (56 days). Multiple doses can be given with acceptable toxicity and pain control, however, only 38% of patients will qualify for multiple treatments.

Eur J Nucl Med 1995 Oct;22(10):1101-4

Bone pain palliation with strontium-89 in breast cancer patients with bone metastases and refractory bone pain.

Berna. Fifteen patients with breast cancer and skeletal metastases who had bone pain refractory to opioid analgesics and who were not eligible for or had not responded to local field radiotherapy, were treated with strontium-89. All patients had received previous treatment with chemotherapy and radiotherapy for bone metastases. Pain relief and a reduction in analgesic requirements were observed in 7 of the 15 (47%) patients, with a reduction in the severity score from 34% to 71%. Duration of the response varied from 3 to 7 months. A decrease in peripheral blood cell count was observed in 11 patients: a 15%-66% reduction in white cell count and a 14%-75% reduction in platelet count were detected at 12 weeks after treatment in these patients.

J Nucl Med 1993 Nov;34(11):1839-44

Samarium-153-EDTMP in bone metastases of hormone refractory prostate carcinoma: a phase I/II trial.

Collins. Fifty-two patients with hormone refractory prostate cancer with bony metastases were treated with doses beginning at 0.5 mCi/kg (18.5 MBq/kg), escalating in 0.5-mCi (18.5 MBq) increments to 3.0 mCi/kg (111 MBq/kg).Pain palliation with a mean duration of 2.6 mo was present in 74% of the patients. Toxicity was exclusively hematologic at the highest dose levels. No infectious or bleeding complications occurred, with 45 of the 52 (86%) patients demonstrating complete hematologic recovery. Patients receiving higher doses had significantly greater reductions in serum prostate specific antigen and serum prostatic acid phosphatase levels. The patients receiving greater doses also showed a trend toward improved survival.

J Nucl Med 1992 Aug;33(8):1451-8

Samarium-153-EDTMP: pharmacokinetic, toxicity and pain response using an escalating dose schedule in treatment of metastatic bone cancer.

Farhanghi Samarium-153 emits medium-energy beta particles and an imageable gamma photon with a physical half-life of 46.3 hr. Myelotoxicity was observed in 10 of the 29 treatment courses and leukopenia occurred in two. In four patients an exacerbation of the pre-existing pain ("flare reaction") was recorded. Pain palliation occurred in 65% of the treated patients (mean: 3.8 mo, range: 1-11 mo). Retreatment in first time responder patients was quite effective.