Originally published as JCO Early Release 10.1200/JCO.2008.20.4164 on April 13 2009

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Phase I Study of Samarium-153 Lexidronam With Docetaxel in Castration-Resistant Metastatic Prostate Cancer

From the Genitourinary Oncology Service and Clinical Immunology Service, Department of Medicine; Nuclear Medicine Service, Department of Radiology; and Departments of Medical Physics and Biostatistics, Memorial Sloan-Kettering Cancer Center; and Department of Medicine, Weill Medical College of Cornell University, New York, NY.

Corresponding author: Michael J. Morris, MD, Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; e-mail: morrism{at}mskcc.org.

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 (¹⁵³Sm) 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/m² and ¹⁵³Sm 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 ¹⁵³Sm-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 ¹⁵³Sm-EDTMP. Patients received an average of 5.6 docetaxel doses (range, one to 13 doses) and 2.9 ¹⁵³Sm-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 ¹⁵³Sm-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.

Supported in part by Cytogen Inc and National Cancer Institute Grant No. CA102544.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00121095.

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