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

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Abstract
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.

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