Samarium-153-Lexidronam Complex For Treatment Of Occult Bony Metastases In High-Risk, Clinically Non-Metastatic Prostate Cancer: The First Report Of A Completed Phase I Trial

We completed a Phase I trial to determine the maximum tolerated dose (MTD) of 153Sm Lexidronam administered with neoadjuvant hormonal therapy (NHT) and external beam radiation therapy (RT) in high-risk clinically non-metastatic prostate cancer. The purpose of this radiotherapeutic approach was to safely and effectively treat subclinical bony metastases with a radiopharmaceutical agent in conjunction with NHT and RT. High-risk M0 prostate cancer patients (PSA >20 ng/mL, Gleason score >7, or >T3) were eligible for this prospective trial of dose-escalated radioactive 153Sm Lexidronam (0.25 mCi/kg to 2.0 mCi/kg). After 1 month of total androgen suppression (TAS), we administered 153Sm Lexidronam followed by 4 more months of TAS, 46.8 Gy to the pelvic region and 23.4 Gy to the prostate target (TD = 70.2 Gy). We serially assessed hematologic and serum chemistry parameters. The primary endpoint was Grade III toxicity or higher according to the NCI Common Toxicity Criteria (CTC). Twenty-nine patients enrolled (median PSA = 8.2 ng/mL, 27/29 (93%) T stage ≥T2b, 24/29 (83%) had Gleason >7) and received 153Sm Lexidronam 0.25 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 any 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. There was a significant dose-response relationship in the mean nadir platelet count at 4 weeks after 153Sm Lexidronam administration (p = 0.023). In the 22 patients with testosterone levels available, there was also a significant difference in hemoglobin level between 5 medically castrated patients (testosterone level <50) and 17 non-castrated patients (p = 0.019), median hemoglobin of 11.4 g/dL in medically castrated patients vs. 13.9 g/dL otherwise. These findings demonstrate that the administration of 153Sm Lexidronam at a MTD of 2 mCi/kg with TAS and RT was safe and feasible in patients with high-risk M0 prostate cancer. A Phase II study to test the efficacy of this treatment paradigm will be conducted by the Radiation Therapy Oncology Group.