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

Introduction: The optimal dose of samarium-153-EDTMP (153Sm-EDTMP) for effective palliation of painful metastases to bone is under investigation. It is not known whether increased doses of 153Sm EDTMP will lead to better and longer pain and tumour control and survival. Multiple dose efficacy and toxicity is of importance as most patients will require prolonged support for pain. Methods: Twenty-eight (28) patients were treated with 0.75 mCi/kg, 35 patients with 1.5 mCi/kg and 19 patients with 3 mCi/kg in three sequential Phase I-II trials. 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). There is no evidence that increasing dose leads to better and longer pain control, tumour response and survival, but toxicity is increased. Multiple doses can be given with acceptable toxicity and pain control, however, only 38% of patients will qualify for multiple treatments. Conclusion: 153Sm-EDTMP provides adequate and safe palliation but multiple doses can only be given in 38% of patients. There is not a clear dose response relationship. The length of pain control is satisfactory but not ideal and hospitalization for 4 days every 6-8 weeks is a disadvantage. Further research is required to combine 153Sm-EDTMP with cytostatics and to administer it on an out patient basis.