Safety analysis of repeated high doses of samarium-153 lexidronam in men with hormone-naive prostate cancer metastatic to bone.

ABSTRACT

PURPOSE: The safety and tolerability of repetitive doses of the boneseeking radiopharmaceutical samarium-153 lexidronam (153Sm- EDTMP) were investigated in men with hormone-naive prostate cancer metastatic to bone. PATIENTS AND METHODS: Within 30 days of initiating androgen deprivation, the first of 4 planned doses of 153Sm- EDTMP given every 12 weeks was administered. Growth factors were not permitted. The first cohort of 6 patients received 153Sm-EDTMP at 2 mCi/kg per dose; 3 patients completed all 4 doses and 3 received 3 doses. RESULTS: There were 7 episodes of grade 3 neutropenia and 1 each of grade 3 and 4 thrombocytopenia. Of 6 patients in the second cohort who received 153Sm-EDTMP 2.5 mCi/kg per dose, only 1 received all 4 doses. Four events of grade 3 neutropenia and 2 events of grade 3 thrombocytopenia were reported. The 12-week dose schedule resulted in persistent low-grade thrombocytopenia and/or leukopenia, which prevented administration of all 4 planned doses. As a result, the dose of 153Sm-EDTMP was decreased to 2 mCi/kg for a total of 3 doses administered every 16 weeks. Five of 6 patients in this cohort received all 3 doses of 153Sm-EDTMP. There were 7 episodes of reversible grade 3 neutropenia. For all 18 patients on the study, there were no drug-related serious adverse events or grade 4 nonhemmatologic toxicities. CONCLUSION: In men with hormone-naive prostate cancer metastatic to bone, the feasible dose and schedule for repeated doses of 153Sm-EDTMP is 2 mCi/kg given every 16 weeks for 3 doses.