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Dose‐finding study of 153 Sm‐EDTMP in patients with poor‐prognosis osteosarcoma
Author(s) -
Loeb David M.,
GarrettMayer Elizabeth,
Hobbs Robert F.,
Prideaux Andrew R.,
Sgouros George,
Shokek Ori,
Wharam Moody D.,
Scott Tammy,
Schwartz Cindy L.
Publication year - 2009
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.24286
Subject(s) - medicine , toxicity , pulmonary toxicity , nuclear medicine , osteosarcoma , refractory (planetary science) , surgery , pathology , physics , astrobiology
BACKGROUND: Samarium‐153 ethylenediaminetetramethylene phosphonic acid ( 153 Sm‐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 153 Sm‐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 153 Sm‐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/mm 3 and a platelet count >75,000/mm 3 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 153 Sm‐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 153 Sm‐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.