Clinical benefit of bone-targeted radiometabolic therapy with 153Sm-EDTMP combined with chemotherapy in patients with metastatic hormone-refractory prostate cancer

Ricci, Sergio; Boni, Giuseppe; Pastina, Ilaria; Genovesi, Dario; Cianci, C.; Chiacchio, Serena; Orlandini, Cinzia; Grosso, M; AlSharif, Abedallatif; Chioni, Aldo; Donato, Samantha Di; Francesca, F.; Selli, Cesare; Rubello, Domenico; Mariani, Giuliano

doi:10.1007/s00259-006-0343-8

Cited by 55 publications

(28 citation statements)

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“…Based on these data, we can infer that an additional dose of Sm-153-EDTMP may be necessary to get the desired pain relief effect when docetaxel is used in combination with this radiopharmaceutical. It was reported that the average duration of bone pain palliation in patients treated with Sm-153-EDTMP alone was about 3-4 months, while it was about 9-10 months in patients who started receiving estramustine phosphate or mitoxantrone plus prednisone after treatment with the bone-seeking radionuclide 12 . However, information about the clinical effect of docetaxel associated to Sm-153-EDTMP is scarce.…”

Section: Discussionmentioning

confidence: 99%

“…It was based on the possibility of using Sm-153-EDTMP combined with docetaxel for the treatment of bone metastasis pain in patients with prostate or breast cancer. Recently, Ricci et al 12 reported that Sm-153-EDTMP is effective in bone pain relief, with minimal toxicity. When administered in combination with chemotherapy (estramustine phosphate or mitoxantrone plus prednisone), it prolonged survival.…”

Section: Discussionmentioning

confidence: 99%

“…The advantages of radiopharmaceutical use include the ease of administration, the ability to treat multiple sites of metastatic disease, the improved potential therapeutic ratio due to bone location and the potential of combining with chemotherapy agents and external beam radiation for an enhanced therapeutic effect 4,5 . A subset of trials has suggested improved pain palliation by combining a radiopharmaceutical agent with chemotherapy 4,5,12 .…”

Section: Discussionmentioning

confidence: 99%

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Biodistribution of samarium-153-EDTMP in rats treated with docetaxel

et al. 2009

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Purpose: Many patients with metastatic bone disease have to use radiopharmaceuticals associated with chemotherapy to relieve bone pain. The aim of this study was to assess the influence of docetaxel on the biodistribution of samarium-153-EDTMP in bones and other organs of rats. Methods: Wistar male rats were randomly allocated into 2 groups of 6 rats each. The DS (docetaxel/samarium) group received docetaxel (15 mg/kg) intraperitoneally in two cycles 11 days apart. The S (samarium/control) group rats were not treated with docetaxel. Nine days after chemotherapy, all the rats were injected with 0.1ml of samarium-153-EDTMP via orbital plexus (25µCi). After 2 hours, the animals were killed and samples of the brain, thyroid, lung, heart, stomach, colon, liver, kidney and both femurs were removed. The percentage radioactivity of each sample (% ATI/g) was determined in an automatic gamma-counter (Wizard-1470, Perkin-Elmer, Finland). Results: On the 9 th day after the administration of the 2 nd chemotherapy cycle, the rats had a significant weight loss (314.50±22.09g) compared (p<0.5) to pre-treatment weight (353.66± 22.8). The % ATI/g in the samples of rats treated with samarium-153-EDTMP had a significant reduction in the right femur, left femur, kidney, liver and lungs of animals treated with docetaxel, compared to the control rats. Conclusion: The combination of docetaxel and samarium-153-EDTMP was associated with a lower response rate in the biodistribution of the radiopharmaceutical to targeted tissues. Further investigation into the impact of docetaxel on biodistribution of samarium-153-EDTMP would complement the findings of this study. Key words: Taxoids. Samarium. Biological Availability. Drug Therapy. Rats. RESUMOObjetivo: Muitos pacientes com metástases ósseas são tratados com radiofármacos associados com quimioterapia para alívio da dor óssea. O objetivo do trabalho foi estudar a influência do docetaxel na biodistribuição do EDTMP-153-samário nos ossos e outros órgãos de ratos. Métodos: Ratos Wistar foram aleatoriamente alocados em 2 grupos de 6 animais cada. O grupo DS (docetaxel/samário) recebeu docetaxel (15 mg/kg) intraperitoneal em dois ciclos com 11 dias de intervalo. Os ratos do grupo S (samário/controle) não foram tratados com docetaxel. Nove dias após a quimioterapia, todos os animais receberam 0,1ml de EDTMP-153-samário via plexo orbital (25µCi). Após 2 horas, os animais foram mortos e feitas biópsias de cérebro, tireóide, pulmão, coração, estômago, cólon, fígado, rim e fêmures. O percentual de radioatividade por grama (%ATI/g) de tecido de cada biópsia foi determinado em contador gama automático (Wizard-1470, Perkin-Elmer, Finland). Resultados: No 9º após 2º ciclo de docetaxel os ratos tiveram perda de peso significante, passando de 353,66± 22,8g (controle/pré-tratamento) para 314,50±22,09g (p<0,5). Os % ATI/g nos órgãos dos ratos tratados com EDTMP-153-samário e docataxel tiveram redução significante nos fêmures direito e esquerdo, rim, fígado e pulmão, quando comparados com os não trata...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Biodistribution of samarium-153-EDTMP in rats treated with docetaxel

et al. 2009

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“…The nadir of platelet and white cell reductions was between 3 to 6 weeks after injection, with complete recovery by week 8-9 (15-18), less delayed and shorter in duration than with 89 Sr. There is no evidence regarding samarium improving OS when used as a single agent but this was hypothesized when 153 Sm is used sequentially or combined with docetaxel (19)(20)(21) or immunotherapy (22).…”

Section: Abstract 223 Ra Prolongs Overall Survival In Symptomatic Pamentioning

confidence: 99%

“…Previous experiences with bone seeking beta-particle emitters are conflicting. Association of 153 Sm-EDTMP with chemotherapy, EBRT and bisphosphonates gave advantages in terms of pain relief (21,40,90).…”

Section: Association Sequence and Interactionsmentioning

confidence: 99%

Radium-223: Insight and Perspectives in Bone-metastatic Castration-resistant Prostate Cancer

Buroni

Persico

Pasi

et al. 2016

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Abstract. 223 Prostate cancer (PCa) is the most common malignancy in men (1). In patients affected by advanced PCa, defined as hormonesensitive disease since the tumor still requires androgen for growth, androgen deprivation therapy (ADT), including luteinizing hormone-releasing hormone (LHRH) agonists, antagonists and anti-androgens, represents the first-line treatment. Unfortunately some cancer cells develop resistance to ADT, indicating the progression of the disease to metastatic castration-resistant prostate cancer (mCRPCa). Such resistance to castration occurs in most patients (2) and, despite the approval of new therapeutic agents, mCRPCa remains a lethal disease (3). Nowadays the new therapeutic landscape for patients affected by mCRPCa aims to extend overall survival (OS) and includes cytotoxic, new-generation anti-androgens, immunotherapeutics and radiopharmaceuticals (4, 5).Bones are the preferred site of metastasis. Almost 90% of men who die from PCa have bone-metastatic disease (6), with a 5-year OS rate of 20%. Due to the fragility of bone with metastases, with the related risk of pain, fractures, spinal cord compression and hematological consequences, several drugs have been developed to treat the osseous involvement of this disease. In previous years, the optimal treatment aimed to relieve pain and reduce skeletal morbidity.Besides systemic therapies, bone-targeted agents that focus their activity on bone, such as bisphosphonates, monoclonal antibody and radiopharmaceuticals, have become available. The bisphosphonate zoledronic acid, the antibody to receptor activator of nuclear factor kappa-B ligand (RANKL) denosumab and radiopharmaceuticals [such as 89 Sr and 153 Sm-ethylene diamine tetramethylene phosphonate ( 153 Sm-EDTMP)], were approved for delaying skeletal-related events (SREs) and for the palliation of bone pain from mCRPCa. Radionuclide TherapyRadionuclide therapy is known to deliver ionizing radiation to tumor sites, thereby killing cancer cells (7). Bone-targeted radiopharmaceuticals localize their radiation to sites of high bone remodeling. 5719

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Synthesis and preclinical pharmacological evaluation of ^99mTc‐TEDP as a novel bone imaging agent

Motaleb

Sakr

2011

Labelled Comp Radiopharmac

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The detection of bone metastasis in early stages requires the development of high-affinity bone imaging radiopharmaceuticals for the improvement of the diagnostic accuracy of routine bone scanning and effective management of these medical cases. This study aimed to provide a convenient synthesis of 1-thioethylidene-l,l-disodiumphosphonate (TEDP) and an improved preparation of its 99m Tc-TEDP complex. The results showed that the radiochemical purity of 99m Tc-TEDP was found to be 95 ± 2% and that its stability was up to 6 h. Biodistribution study showed high and long uptake of 99m Tc-TEDP in bone starting from 15 min (39 ± 4 ID/g) to 3 h (53 ± 2.4 ID/g) showing high affinity of 99m Tc-TEDP complex to bones. This research could introduce a novel radiopharmaceutical that could be used in scanning body bones starting from 15 min between injection of 99m Tc-TEDP and bone imaging, minimizing the burden on patients in terms of the total length of the examination and the dose of radiation absorbed and showing high specificity and efficacy in bone scintigraphy.

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Clinical benefit of bone-targeted radiometabolic therapy with 153Sm-EDTMP combined with chemotherapy in patients with metastatic hormone-refractory prostate cancer

Cited by 55 publications

References 27 publications

Biodistribution of samarium-153-EDTMP in rats treated with docetaxel

Biodistribution of samarium-153-EDTMP in rats treated with docetaxel

Radium-223: Insight and Perspectives in Bone-metastatic Castration-resistant Prostate Cancer

Synthesis and preclinical pharmacological evaluation of ^99mTc‐TEDP as a novel bone imaging agent

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Clinical benefit of bone-targeted radiometabolic therapy with 153Sm-EDTMP combined with chemotherapy in patients with metastatic hormone-refractory prostate cancer

Cited by 55 publications

References 27 publications

Biodistribution of samarium-153-EDTMP in rats treated with docetaxel

Biodistribution of samarium-153-EDTMP in rats treated with docetaxel

Radium-223: Insight and Perspectives in Bone-metastatic Castration-resistant Prostate Cancer

Synthesis and preclinical pharmacological evaluation of 99mTc‐TEDP as a novel bone imaging agent

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Synthesis and preclinical pharmacological evaluation of ^99mTc‐TEDP as a novel bone imaging agent