Tandem Dosing of Samarium-153 Ethylenediamine Tetramethylene Phosphoric Acid With Stem Cell Support for Patients With High-Risk Osteosarcoma

Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21231, USA.
Cancer (Impact Factor: 4.9). 12/2010; 116(23):5470-8. DOI: 10.1002/cncr.25518
Source: PubMed

ABSTRACT Samarium-153 ethylenediamine tetramethylene phosphoric acid (153Sm-EDTMP) is a radiopharmaceutical that has been used to treat osteosarcoma. The authors conducted a phase 2 study to test safety and response of high-risk osteosarcoma to tandem doses of 153Sm-EDTMP and to determine correlation between radiation delivered by low and high administered activities.
Patients with recurrent, refractory osteosarcoma detectable on standard 99mTc bone scan received a low dose of 153Sm-EDTMP (37.0-51.8 MBq/kg), followed upon count recovery by a second, higher dose (222 MBq/kg). Fourteen days later, patients were rescued with autologous hematopoietic stem cells. The authors assessed response to therapy, performed dosimetry to determine the relationship between administered activity and tumor absorbed dose, and investigated whether changes in 2-(fluorine-18) fluoro-2-deoxy-d-glucose (18F-FDG) tumor uptake upon hematologic recovery reflected disease response.
Nine patients were given tandem doses of 153Sm-EDTMP; 2 received only the initial dose because of disease progression. Six patients experienced radiographic disease stabilization, but this was not considered a response, so the study was terminated early. There was a linear relationship between administered activity and tumor absorbed dose, but there was no correlation between change in 18F-FDG positron emission tomography tumor uptake and tumor absorbed dose or time to progression. The median time to progression for the entire group was 79 days.
Tandem doses of 153Sm-EDTMP were safe for this cohort of heavily pretreated patients with very high-risk disease. The strong correlation between absorbed dose and administered activity within each evaluable patient provides a methodology to individually tailor tandem doses of this agent.

Download full-text


Available from: Allen Chen, Jul 04, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Primary malignant bone tumours, osteosarcomas, and Ewing sarcomas are rare diseases which occur mainly in adolescents and young adults. With the current therapies, some patients remain very difficult to treat, such as tumour with poor histological response to preoperative CT (or large initial tumour volume for Ewing sarcomas not operated), patients with multiple metastases at or those who relapsed. In order to develop new therapies against these rare tumours, we need to unveil the key driving factors and molecular abnormalities behind the malignant characteristics and to broaden our understanding of the phenomena sustaining the metastatic phenotype and treatment resistance in these tumours. In this paper, starting with the biology of these tumours, we will discuss potential therapeutic targets aimed at increasing local tumour control, limiting metastatic spread, and finally improving patient survival.
    Sarcoma 01/2012; 2012:301975. DOI:10.1155/2012/301975
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Primary and metastatic malignant bone lesions result in significant pain and disability in oncology patients. Targeted bone-seeking radioisotopes including 153 Samarium ethylene-diamine-tetramethylene-phosphonic acid (153 Sm-EDTMP) have been shown to effectively palliate bone pain, often when external beam radiotherapy (EBRT) is not feasible. However, recent evidence also suggests 153 Sm-EDTMP has cytotoxic activity either alone or in combination with chemotherapy or EBRT. 153 Sm-EDTMP may be useful as anti-neoplastic therapy apart from pain palliation in a variety of malignancies. For prostate cancer patients, several phase I and II clinical trials have shown that combined 153 Sm-EDTMP and docetaxel-based chemotherapy can result in >50% decrease in prostate-specific antigen with manageable myelosuppression. In hematologic malignancies, 153 Sm-EDTMP produced clinical responses when combined with bortezomib in multiple myeloma. 153 Sm-EDTMP also can be used with myeloablative chemotherapy for marrow conditioning prior to stem cell transplant. In osteosarcoma, 153 Sm-EDTMP infusion delivers radiation to multiple unresectable lesions simultaneously and provides local cytotoxicity without soft tissue damage that can be combined with chemotherapy or radiation. Prior to routine incorporation of 153 Sm-EDTMP into therapeutic regimens, we must learn how to ensure optimal delivery to tumors, determine which patients are likely to benefit, improve our ability to assess clinical response in bone lesions and further evaluate the efficacy of 153 Sm-EDTMP in combination with chemotherapy, radiation and novel targeted agents. Copyright: © 2012 Wilky BA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
    01/2012; S1(002). DOI:10.4172/2161-1459.S1-002
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: (153)Sm-ethylenediamine tetramethylene phosphonic acid ((153)Sm-EDTMP) therapy for osteosarcoma is being investigated. In this study, we analyzed the influence of (153)Sm-EDTMP administered activity (AA), osteosarcoma tumor density, mass, and the shape of the tumor on absorbed dose (AD). We also studied the biologic implication of the nonuniform tumor AD distribution using radiobiologic modeling and examined the relationship between tumor AD and response. Nineteen tumors in 6 patients with recurrent, refractory osteosarcoma enrolled in a phase I or II clinical trial of (153)Sm-EDTMP were analyzed using the 3-dimensional radiobiologic dosimetry (3D-RD) software package. Patients received a low dose of (153)Sm-EDTMP (37.0-51.8 MBq/kg), followed on hematologic recovery by a second, high dose (222 MBq/kg). Treatment response was evaluated using either CT or MRI after each therapy. SPECT/CT of the tumor regions were obtained at 4 and 48 h or 72 h after (153)Sm-EDTMP therapy for 3D-RD analysis. Mean tumor AD was also calculated using the OLINDA/EXM unit-density sphere model and was compared with the 3D-RD estimates. On average, a 5-fold increase in the AA led to a 4-fold increase in the mean tumor AD over the high- versus low-dose-treated patients. The range of mean tumor AD and equivalent uniform dose (EUD) for low-dose therapy were 1.48-14.6 and 0.98-3.90 Gy, respectively. Corresponding values for high-dose therapy were 2.93-59.3 and 1.89-12.3 Gy, respectively. Mean tumor AD estimates obtained from OLINDA/EXM were within 5% of the mean AD values obtained using 3D-RD. On an individual tumor basis, both mean AD and EUD were positively related to percentage tumor volume reduction (P = 0.031 and 0.023, respectively). The variations in tumor density, mass, and shape seen in these tumors did not affect the mean tumor AD estimation significantly. The tumor EUD was approximately 2- and 3-fold lower than the mean AD for low- and high-dose therapy, respectively. A dose-response relationship was observed for transient tumor volume shrinkage.
    Journal of Nuclear Medicine 02/2012; 53(2):215-24. DOI:10.2967/jnumed.111.096677 · 5.56 Impact Factor