A DOSE-CONTROLLED STUDY OF SM-153-ETHYLENEDIAMINETETRAMETHYLENEPHOSPHONATE (EDTMP) IN THE TREATMENT OF PATIENTS WITH PAINFUL BONE METASTASES

One hundred and fourteen patients with painful bone metastases partici pated in this randomised, dose-controlled study of the efficacy and sa fety of Sm-153-ethylenediaminetetramethylenephosphonate (EDTMP), a sys temically administered radiopharmaceutical. Fifty-five patients receiv ed single doses of 0.5 mCi/kg and 59 patients received single doses of 1.0 mCi/kg. Treatment with Sm-153-EDTMP produced improvement from bas eline in all patient-rated efficacy assessments, including degree of p ain, level of daytime discomfort, quality of sleep and pain relief. Du ring the first 4 weeks after dose administration, when the patients ev aluated efficacy daily, there were statistically significant changes f rom baseline with the 1.0 mCi/kg dose but not with the 0.5 mCi/kg dose . The difference between doses in visual analogue pain scores was stat istically significant at week 4 (P = 0.0476). Among subsets of patient s examined, female patients with breast cancer receiving 1.0 mCi/kg ha d the most noticeable improvement. The physicians judged that approxim ately half of the patients in each dose group were experiencing some d egree 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 patien ts in the higher dose group (54%) than in the lower dose group (44%) c ompleted the 16-week study. A predictable level of dose-related marrow suppression was the only toxicity associated with Sm-153-EDTMP treatm ent. 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 pat ients than in male patients. Long-term follow-up revealed longer survi val 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 Sm-153-EDTMP is safe and effective for the tre atment of painful bone metastases. (C) 1997 Elsevier Science Ltd.