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.

• Authors: Celestia S Higano, Donald P Quick, David Bushnell, Oliver Sartor
• Journal: Clinical genitourinary cancer (Clin Genitourin Cancer) Vol. 6 Issue 1 Pg. 40-5 (Mar 2008) ISSN: 1558-7673 [Print] United States
• PMID: 18501082 (Publication Type: Journal Article)

Chemical References

• Analgesics, Non-Narcotic
• Organometallic Compounds
• Organophosphorus Compounds
• Samarium
• samarium Sm-153 lexidronam

Topics

• Adenocarcinoma (drug therapy, secondary)
• Aged
• Aged, 80 and over
• Analgesics, Non-Narcotic (administration & dosage)
• Bone Neoplasms (drug therapy, secondary)
• Dose-Response Relationship, Drug
• Feasibility Studies
• Humans
• Male
• Middle Aged
• Neoplasms, Hormone-Dependent (pathology, therapy)
• Organometallic Compounds (administration & dosage)
• Organophosphorus Compounds (administration & dosage)
• Prostatic Neoplasms (pathology, therapy)
• Samarium
• Survival Rate