A phase I study of combined docetaxel and repeated high activity 186Re-HEDP in castration-resistant prostate cancer (CRPC) metastatic to bone (the TAXIUM trial)

Jong, Joyce M. van Dodewaard-de; Klerk, John M. H. de; Bloemendal, Haiko J.; Bezooijen, Bart P. J. van; Haas, Marie J. de; Wilson, Richard H.; O’Sullivan, Joe M.

doi:10.1007/s00259-011-1883-0

Cited by 28 publications

(11 citation statements)

References 19 publications

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“…This observation may be consistent with the finding that the moderate accumulation of 188 Re-liposome in orthotopic lung cancer cells was not sufficient to cause tumor death but did suppress tumor growth. Several lines of evidence have shown that the combination of 188 Re and chemotherapy or multiple dosages of 188 Re may increase the cytotoxic response in various cancers (21,28,32). It would be advantageous to design different regimes to evaluate whether 188 Re-liposome treatment can eradicate NSCLC and reach maximum therapeutic efficacy.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome–Embedded ¹⁸⁸Re on Human Non–Small Cell Lung Cancer Using an Orthotopic Small-Animal Model

Lin

Chang

et al. 2014

J Nucl Med

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Non-small cell lung cancer (NSCLC) is a highly morbid and mortal cancer type that is difficult to eradicate using conventional chemotherapy and radiotherapy. Little is known about whether radionuclide-based pharmaceuticals can be used for treating NSCLC. Here we embedded the therapeutic radionuclide 188 Re in PEGylated (PEG is polyethylene glycol) liposomes and investigated the biodistribution, pharmacokinetics, and therapeutic efficacy of this nanoradiopharmaceutical on NSCLC using a xenograft lung tumor model and the reporter gene imaging techniques. Methods: Human NSCLC NCI-H292 cells expressing multiple reporter genes were used in this study. 188 Re was conjugated to N,N-bis(2-mercaptoethyl)-N′,N′-diethylethylenediamine (BMEDA) and loaded into the PEGylated liposome to form a 188 Reliposome. The tumor growth rates and localizations were confirmed using bioluminescent imaging and SPECT/CT after the 188 Re-BMEDA or 188 Re-liposome was intravenously injected. The accumulation of the nanodrug in various organs was determined by the biodistribution analysis and the nano-SPECT/CT system. The pharmacokinetic and dosimetric analyses were further determined using WinNonlin and OLINDA/EXM, respectively. Results: The biodistribution and nano-SPECT/CT imaging showed that PEGylated 188 Re-liposome could efficiently accumulate in xenograft tumors formed by NCI-H292 cells that were subcutaneously implanted in nude mice. Pharmacokinetic analysis also showed that the retention of 188 Re-liposome was longer than that of 188 Re-BMEDA. In an orthotopic tumor model, ex vivo γ counting revealed that the uptake of 188 Re-liposome was detected in tumor lesions but not in surrounding normal lung tissues. Moreover, we evaluated the therapeutic efficacy using bioluminescent imaging and showed that the lung tumor growth was suppressed but not eradicated by 188 Re-liposome. The life span of 188 Re-liposometreated mice was 2-fold longer than that of untreated control mice. Conclusion:The results of biodistribution, pharmacokinetics, estimated dosimetry, nano-SPECT/CT, and bioluminescent imaging suggest that the PEGylated liposome-embedded 188 Re could be used for the treatment of human lung cancers.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome–Embedded ¹⁸⁸Re on Human Non–Small Cell Lung Cancer Using an Orthotopic Small-Animal Model

Lin

Chang

et al. 2014

J Nucl Med

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“…In fact, bone marrow suppression and the subsequent adverse effects could be affected by various factors other than the dose administered. Suggested factors include the patient's overall condition, metastatic load, pretreatment blood cell count, and previous therapies (28,29). Our study showed that declines in blood cell count do not depend solely on the dose administered and that baseline complete blood count is important when selecting the best treatment.…”

Section: Discussionmentioning

confidence: 79%

Phase 2 Study of a High Dose of 186Re-HEDP for Bone Pain Palliation in Patients with Widespread Skeletal Metastases

Pirayesh

Amoui

Mirzaee

et al. 2013

Journal of Nuclear Medicine Technology

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186 Re-1-hydroxyethylidene-1,1-diphosphonate (HEDP) is an attractive radiopharmaceutical for the treatment of bone pain arising from skeletal metastatic lesions. Currently, 186 Re-HEDP is most commonly used in European countries. The aim of this study was to investigate the palliative efficacy and adverse effects of 186 Re-HEDP in patients with different types of cancers and skeletal bone pain. Methods: Nineteen (8 male, 11 female) patients with various cancers (breast, prostate, renal cell carcinoma, colon, and neuroendocrine tumors) and painful bone metastases were included in the study. A dose of 1,480-3,330 MBq (40-90 mCi) of 186 Re-HEDP was administered intravenously. The patients' level of pain relief was assessed by the Visual Analog Scale for 8 wk after treatment and by a weekly blood cell count to evaluate for hematologic toxicity. Results: The overall response rate was 89.5%, and the mean pain score assessed by the Visual Analog Scale was reduced from 9.1 to 5.3 after 1 wk (P 5 0.003). No adverse effects were reported by patients during intravenous administration or for up to 24 h after administration. A flare reaction was seen in 63.2% of patients, mainly during days 1-3, and lasted for 2-4 d. There was no significant correlation between the response to therapy and the flare reactions (P . 0.05). The nadir of platelet reduction occurred at the fourth or fifth week and led to platelet infusion in only 4 patients with a low baseline platelet count and diffuse skeletal metastases. Bone marrow suppression occurred in patients receiving higher doses, but no clinical problems were seen except in 2 patients who required packed cell transfusion similar to their prior transfusions. Conclusion: 186 Re-HEDP is an effective radiopharmaceutical for the palliative treatment of metastatic bone pain and has minimal adverse effects.Key Words: rhenium 186(tin) etidronate; pain palliation; bone metastasis Nucl Med Technol 2013; 41:192-196 DOI: 10.2967/jnmt.113.124297 The skeleton is the most common site of metastatic disease, and tumors arising from the breast, prostate, lung, thyroid, and kidney commonly spread to bone. The frequency of bone metastases has been estimated at 65%-75% in patients with breast and prostate cancer (1,2) and about 30%-40% in those with lung cancer (3). Bone pain, as the main symptom of skeletal metastases and the most common type of cancer-related pain, obviously has a negative impact on quality of life (4). Currently, the factors contributing to cancer pain are not completely understood (5,6), and metastatic bone pain might be poorly localized for external radiation therapy (7). Various modalities have been introduced for the treatment of bone metastases, including analgesics, hormone therapy, cytotoxic drugs, biphosphonates, and surgery; however, they are not effective in all patients with painful refractory skeletal metastases. An alternative approach is systemic administration of radiopharmaceuticals, which is a valuable and effective method for relieving bone pain in patients with ...

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“…At absorbed doses that are equivalent to those of low-LET radiation, high-LET particles are more cytotoxic. This phenomenon is called “radiation quality.” Most of the radionuclides used in internal radiotherapy; such as iodine-131 (Grunwald and Ezziddin, 2010; Leahy and Turner, 2011), yttrium-90 (Kulik et al, 2008; Menda et al, 2010; Kunikowska et al, 2011), lutetium-177 (Gains et al, 2011; Kunikowska et al, 2011), 188 Re (Kumar et al, 2007; Torres-Garcia et al, 2008), or rhenium-186 (Syed et al, 2006; van Dodewaard-de Jong et al, 2011); emit low-LET radiation of 0.2 keV/μm in the form of β-particles as well as internal conversion electrons (Milenic et al, 2004). High-LET particle emitters used in internal radiotherapy only include the α-emitters bismuth-213, bismuth-212, and astatine-211, as well as lead-212 and actinium-225, which generate bismuth-212 and bismuth-213, respectively.…”

Section: Radionuclides For Nanovectorized Radiotherapymentioning

confidence: 99%

Nanovectorized radiotherapy: a new strategy to induce anti-tumor immunity

Vanpouille-Box¹,

Hindré²

2012

Front. Oncol.

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Recent experimental findings show that activation of the host immune system is required for the success of chemo- and radiotherapy. However, clinically apparent tumors have already developed multiple mechanisms to escape anti-tumor immunity. The fact that tumors are able to induce a state of tolerance and immunosuppression is a major obstacle in immunotherapy. Hence, there is an overwhelming need to develop new strategies that overcome this state of immune tolerance and induce an anti-tumor immune response both at primary and metastatic sites. Nanovectorized radiotherapy that combines ionizing radiation and nanodevices, is one strategy that could boost the quality and magnitude of an immune response in a predictable and designable fashion. The potential benefits of this emerging treatment may be based on the unique combination of immunostimulatory properties of nanoparticles with the ability of ionizing radiation to induce immunogenic tumor cell death. In this review, we will discuss available data and propose that the nanovectorized radiotherapy could be a powerful new strategy to induce anti-tumor immunity required for positive patient outcome.

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A phase I study of combined docetaxel and repeated high activity 186Re-HEDP in castration-resistant prostate cancer (CRPC) metastatic to bone (the TAXIUM trial)

Cited by 28 publications

References 19 publications

Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome–Embedded ¹⁸⁸Re on Human Non–Small Cell Lung Cancer Using an Orthotopic Small-Animal Model

Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome–Embedded ¹⁸⁸Re on Human Non–Small Cell Lung Cancer Using an Orthotopic Small-Animal Model

Phase 2 Study of a High Dose of 186Re-HEDP for Bone Pain Palliation in Patients with Widespread Skeletal Metastases

Nanovectorized radiotherapy: a new strategy to induce anti-tumor immunity

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A phase I study of combined docetaxel and repeated high activity 186Re-HEDP in castration-resistant prostate cancer (CRPC) metastatic to bone (the TAXIUM trial)

Cited by 28 publications

References 19 publications

Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome–Embedded 188Re on Human Non–Small Cell Lung Cancer Using an Orthotopic Small-Animal Model

Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome–Embedded 188Re on Human Non–Small Cell Lung Cancer Using an Orthotopic Small-Animal Model

Phase 2 Study of a High Dose of 186Re-HEDP for Bone Pain Palliation in Patients with Widespread Skeletal Metastases

Nanovectorized radiotherapy: a new strategy to induce anti-tumor immunity

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Product

Resources

About

Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome–Embedded ¹⁸⁸Re on Human Non–Small Cell Lung Cancer Using an Orthotopic Small-Animal Model

Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome–Embedded ¹⁸⁸Re on Human Non–Small Cell Lung Cancer Using an Orthotopic Small-Animal Model