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J Clin Oncol. 2009 May 20;27(15):2436-42. doi: 10.1200/JCO.2008.20.4164. Epub 2009 Apr 13.

Phase I study of samarium-153 lexidronam with docetaxel in castration-resistant metastatic prostate cancer.

Author information

1
Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. morrism@mskcc.org

Erratum in

  • J Clin Oncol. 2011 Oct 10;29(29):3947-8.

Abstract

PURPOSE:

Early studies of patients with castration-resistant metastatic prostate cancer (CRMPC) suggest that chemotherapy administered with a dose of a bone-seeking radiopharmaceutical is superior to chemotherapy alone. To build on this strategy and fully integrate a repetitively dosed bone-seeking radiopharmaceutical into a contemporary chemotherapy regimen, we conducted a phase I study of docetaxel and samarium-153 ((153)Sm) lexidronam.

PATIENTS AND METHODS:

Men with progressive CRMPC were eligible. Cohorts of three to six patients were defined by dose escalations as follows: docetaxel 65, 70, 75, 75, 75 mg/m(2) and (153)Sm ethylenediaminetetramethylenephosphonate (EDTMP) 0.5, 0.5, 0.5, 0.75, 1 mCi/kg. Each cycle lasted a minimum of 6 (cohorts 1 through 5) or 9 (cohort 6) weeks. Docetaxel was administered on days 1 and 22 (and day 43 for cohort 6), and (153)Sm-EDTMP was administered on day -1 to 1 of each cycle. Patients with acceptable hematologic toxicities were eligible to receive additional cycles until progression.

RESULTS:

Twenty-eight men were treated in six cohorts. Maximum-tolerated dose was not reached, because full doses of both agents were well tolerated, even using an every-6-week dosing schedule of (153)Sm-EDTMP. Patients received an average of 5.6 docetaxel doses (range, one to 13 doses) and 2.9 (153)Sm-EDTMP doses (range, one to six doses). Fifteen patients demonstrated a more than 50% decline in prostate-specific antigen. Treatment significantly reduced indices of bone deposition and resorption.

CONCLUSION:

Docetaxel and (153)Sm-EDTMP can be combined safely at full doses over repeated cycles. Responses were seen in the small group of patients with taxane-resistant disease tested. The optimal phase II doses for patients with taxane-naïve disease may differ from those optimal for patients with taxane-resistant disease.

PMID:
19364960
PMCID:
PMC2684850
DOI:
10.1200/JCO.2008.20.4164
[Indexed for MEDLINE]
Free PMC Article

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