Dose‐finding study of 153Sm‐EDTMP in patients with poor‐prognosis osteosarcoma

• Published in: Cancer Vol. 115; no. 11; pp. 2514 - 2522
• Main Authors: Loeb, David M., Garrett‐Mayer, Elizabeth, Hobbs, Robert F., Prideaux, Andrew R., Sgouros, George, Shokek, Ori, Wharam, Moody D., Scott, Tammy, Schwartz, Cindy L.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.06.2009; Wiley-Blackwell
• Subjects: Adolescent; Adult; Biological and medical sciences; Blood Cell Count; bone neoplasm; Bone Neoplasms - radiotherapy; Child; Diseases of the osteoarticular system; Female; Humans; Male; Maximum Tolerated Dose; Medical sciences; Neutropenia - etiology; Organometallic Compounds - administration & dosage; Organometallic Compounds - adverse effects; Organophosphorus Compounds - administration & dosage; Organophosphorus Compounds - adverse effects; osteosarcoma; Osteosarcoma - radiotherapy; Prognosis; Radiometry; radiopharmaceuticals; Radiotherapy Dosage; targeted radiotherapy; Thrombocytopenia - etiology; Treatment Outcome; Tumors; Tumors of striated muscle and skeleton; Human; Prognosis; Targeting; Sarcoma; targeted radiotherapy; Diseases of the osteoarticular system; Malignant tumor; Radiotherapy; Osteoarticular system; radiopharmaceuticals; Cancerology; Treatment; Osteosarcoma; Bone; bone neoplasm; Radioisotopic product; Dose; Cancer
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.24286

BACKGROUND: Samarium‐153 ethylenediaminetetramethylene phosphonic acid (153Sm‐EDTMP) has been used to treat patients with high‐risk osteosarcoma. The purpose of the current study was to determine the maximally tolerated dose of 153Sm‐EDTMP that permits hematopoietic recovery within 6 weeks. METHODS: Patients with recurrent or refractory osteosarcoma with bone metastases were enrolled in this study. Subjects were treated with increasing doses of 153Sm‐EDTMP, beginning with 1.0 millicuries (mCi)/kg and followed initially with 40% increment dose level escalations, using a continual reassessment method for dose escalation and de‐escalation with a target dose–limiting toxicity (DLT) rate of 30%. Complete blood counts were monitored weekly, and the primary DLT was defined as failure to achieve an absolute neutrophil count >750/mm3 and a platelet count >75,000/mm3 within 6 weeks of treatment. In addition to assessing toxicity, dosimetry measurements were made to estimate the radiation dose delivered to target lesions. RESULTS: The maximally tolerated dose of 153Sm‐EDTMP was 44.8 megabecquerel (MBq)/kg (1.21 mCi/kg). DLTs were confined to hematologic toxicities, particularly delayed platelet recovery in 2 patients treated at a dose of 51.8 MBq/kg (1.4 mCi/kg). Grade 2 and 3 pulmonary toxicity (graded according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) as reported in 2 patients (at administered activities of 44.8 MBq/kg and 51.8 MBq/kg) was attributable to progressive pulmonary disease. No other significant nonhematologic toxicities were observed. CONCLUSIONS: Patients with osteosarcoma who have previously been heavily treated with chemotherapy can be safely administered 153Sm‐EDTMP with rapid hematologic recovery. The data from the current study support the development of a future trial to assess the efficacy of combining targeted radiotherapy with cytotoxic chemotherapy as a treatment option for patients with high‐risk osteosarcoma. Cancer 2009. © 2009 American Cancer Society. In the current study, samarium‐153 ethylenediaminetetramethylene phosphonic acid was safely administered to heavily pretreated patients with high‐risk osteosarcoma in a dose that allowed for reliable hematopoietic recovery within 6 weeks. A significant fraction of patients experienced temporary disease stabilization.