A Phase I Trial of Samarium-153-Lexidronam Complex for Treatment of Clinically Nonmetastatic High-Risk Prostate Cancer: First Report of a Completed Study

Abstract

We completed a Phase I trial to determine the maximum tolerated dose of samarium-153 EDTMP (153Sm) with hormonal therapy (HT) and radiation therapy (RT) in high-risk clinically nonmetastatic prostate cancer. High-risk M0 prostate cancer patients (prostate-specific antigen>20 ng/mL, Gleason score>7, or>T3) were eligible for this prospective trial of dose-escalated radioactive 153Sm-EDTMP (.25-2.0 mCi/kg) as primary or postoperative therapy. After 1 month of HT, we administered 153Sm-EDTMP followed by 4 more months of HT, 46.8 Gy to the pelvic region and 23.4 Gy to the prostate target (TD=70.2 Gy). The primary endpoint was Grade III toxicity or higher by the National Cancer Institute Common Toxicity Criteria. Twenty-nine patients enrolled (median prostate-specific antigen=8.2 ng/mL, 27/29 (93%) T stage≥T2b, 24/29 (83%) had Gleason>7) and received 153Sm-EDTMP (.25 mCi/kg, 4 patients; 0.5 mCi/kg, 4 patients; 0.75 mCi/kg, 6 patients; 1.0 mCi/kg, 6 patients; 1.5 mCi/kg, 5 patients; 2.0 mCi/kg, 4 patients). Twenty-eight patients underwent all planned therapy without delays (1 patient required surgery before the start of RT). With a median follow-up time of 23 months, there were 2 patients (7%) experiencing Grade III hematologic toxicity. There were no other Grade III or IV side effects. Our trial demonstrates that 2 mCi/kg 153Sm -EDTMP with HT and RT was safe and feasible in men with high-risk M0 prostate cancer. A Phase II study to test this treatment is currently underway by the Radiation Therapy Oncology Group.