Originally published as JCO Early Release 10.1200/JCO.2008.20.5393 on May 4 2009

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Phase I Study of Concurrent Weekly Docetaxel and Repeated Samarium-153 Lexidronam in Patients With Castration-Resistant Metastatic Prostate Cancer

From the Departments of Genitourinary Medical Oncology, Biostatistics and Applied Mathematics, and Nuclear Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX.

Corresponding author: Shi-Ming Tu, MD, Department of Genitourinary Medical Oncology, Unit 1374, The University of Texas M. D. Anderson Cancer Center, P.O. Box 301439, Houston, TX 77239-1439; e-mail: stu{at}mdanderson.org.

Purpose Samarium-153 (¹⁵³Sm) lexidronam is a bone-targeting radiopharmaceutical with a short physical half-life and a favorable toxicity profile. We evaluated the safety and feasibility of a concurrent combination of weekly docetaxel with repeated ¹⁵³Sm-lexidronam in patients with castration-resistant prostate cancer (CRPC).

Patients and Methods A conventional 3 + 3 dose-escalation design was used for this study. Patients were treated in three cohorts comprising two cycles of weekly docetaxel at 25, 30, and 35 mg/m², respectively, on days 1, 8, and 15 of a 28-day cycle in combination with ¹⁵³Sm (1 mCi/kg) on day 1. Unacceptable hematologic toxicity (UHT) was defined as more than 7 days delay in therapy for inadequate counts: an absolute neutrophil count (ANC) more than 1,000/µL and platelets more than 70,000/µL were required at days 8 and 15 and ANC more than 1,500/µL and platelets more than 100,000/µL were required at cycle 2, day 1. If counts had not recovered by day 56 of either combination cycle, UHT was declared.

Results Eighteen patients were treated in three cohorts. Two patients in separate cohorts experienced UHT; the maximum-tolerated dose for this regimen was not reached. The median interval between ¹⁵³Sm doses was 35 days (range, 27 to 57 days). The only significant toxicity was mild, transient myelosuppression. Five patients (28%) experienced grade 3 hematologic toxicity. There were no grade 4 hematologic or nonhematologic toxicities.

Conclusion Two dosing cycles consisting of weekly docetaxel and monthly ¹⁵³Sm-lexidronam were well tolerated and feasible in this CRPC population.

Supported in part by Cytogen Corporation, which also supplied ¹⁵³Sm-lexidronam free of charge for participating patients.

Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL.

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

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