BACKGROUND: β-emitting bone-seeking radiopharmaceuticals have historically been administered for pain palliation whereas docetaxel prolongs life in patients with metastatic castration-resistant prostate cancer (mCRPC).
In combination, these agents simultaneously target the bone stroma and cancer cell to optimize antitumor effects. The toxicity and efficacy when each agent is combined at full, recommended doses, in a repetitive fashion is not well established.
METHODS: Patients with progressive mCRPC and ≥3 bone lesions received 153 Sm-EDTMP (samarium-153 ethylene diamine tetramethylene phosphonate) at a dose of 1.0 mCi/kg every 9 weeks and docetaxel at a dose of 75 mg/m2 every 3 weeks. In the absence of unacceptable toxicity, patients were allowed to continue additional cycles, defined by 9 weeks of treatment, until intolerance or biochemical/radiographic disease progression.
RESULTS: Of the 30 patients treated, approximately 50% were considered to be taxane-naive, 36.7% were taxane-refractory, and 13.3% had previously been exposed to taxanes but were not considered refractory. Patients received on average 2.5 cycles of treatment (6.5 doses of docetaxel and 2.5 doses of 153 Sm-EDTMP). Twelve patients (40%) demonstrated a decline in their prostate-specific antigen level of ≥50%. The median progression-free survival (biochemical or radiographic) was 7.0 months and the overall survival was 14.3 months. Nine patients (30%) did not recover platelet counts >100 K/mm3 after a median of 3 cycles to allow for additional treatment, with 4 patients experiencing prolonged thrombocytopenia. The most common reasons for trial discontinuation were progressive disease and hematologic toxicity.
CONCLUSIONS: The results of the current study indicate that 153 Sm-EDTMP can be safely combined with docetaxel at full doses on an ongoing basis in patients with mCRPC. Although thrombocytopenia limited therapy for some patients, preliminary efficacy supports the strategy of combining a radiopharmaceutical with chemotherapy, which is an appealing strategy given the anticipated availability of α emitters that can prolong survival.
Written by:
Autio KA, Pandit-Taskar N, Carrasquillo JA, Stephenson RD, Slovin SF, Rathkopf DE, Hong C, Heller G, Scher HI, Larson SM, Morris MJ. Are you the author?
Genitourinary Oncology Service, Sidney Kimmel Center for Prostate and Urologic Cancers, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
Reference: Cancer. 2013 Jun 13. Epub ahead of print.
doi: 10.1002/cncr.28103
PubMed Abstract
PMID: 23765638
