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

PURPOSE:

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.

METHODS AND MATERIALS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Richard K Valicenti, Edouard Trabulsi, Charles Intenzo, Jorosali Lavarino, Yihuan Xu, Inna Chervoneva
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 79 Issue 3 Pg. 732-7 (Mar 01 2011) ISSN: 1879-355X [Electronic] United States
• PMID: 20399029 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Published by Elsevier Inc.

Chemical References

• Organometallic Compounds
• Organophosphorus Compounds
• samarium Sm-153 lexidronam
• Prostate-Specific Antigen

Topics

• Aged
• Aged, 80 and over
• Combined Modality Therapy (methods)
• Feasibility Studies
• Humans
• Leukopenia (chemically induced)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Staging
• Organometallic Compounds (administration & dosage, adverse effects)
• Organophosphorus Compounds (administration & dosage, adverse effects)
• Prospective Studies
• Prostate-Specific Antigen (blood)
• Prostatectomy
• Prostatic Neoplasms (blood, drug therapy, pathology, radiotherapy, surgery)
• Radiotherapy Dosage
• Thrombocytopenia (chemically induced)