Phase I study of concurrent weekly docetaxel and repeated samarium-153 lexidronam in patients with castration-resistant metastatic prostate cancer

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.