For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
55
views
286
references
 Top references
cited by
177
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      578
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Radiopharmaceutical therapy in cancer: clinical advances and challenges

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Radiopharmaceutical therapy (RPT) is emerging as a safe and effective targeted approach to treating many types of cancer. In RPT, radiation is systemically or locally delivered using pharmaceuticals that either bind preferentially to cancer cells or accumulate by physiological mechanisms. Almost all radionuclides used in RPT emit photons that can be imaged, enabling non-invasive visualization of the biodistribution of the therapeutic agent. Compared with almost all other systemic cancer treatment options, RPT has shown efficacy with minimal toxicity. With the recent FDA approval of several RPT agents, the remarkable potential of this treatment is now being recognized. This Review covers the fundamental properties, clinical development and associated challenges of RPT.

          Abstract

          Radiopharmaceutical therapy is emerging as a safe and effective approach for the treatment of cancer, offering several advantages over existing therapeutic strategies. Here, Sgouros and colleagues provide an overview of the fundamental properties of radiopharmaceutical therapy, discuss agents in use and in clinical development and highlight the associated translational challenges.

          Related collections

          Most cited references286

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Estimation of clinical trial success rates and related parameters

          Chi Heem Wong, Kien Wei Siah, Andrew Lo (2018)
          SUMMARY Previous estimates of drug development success rates rely on relatively small samples from databases curated by the pharmaceutical industry and are subject to potential selection biases. Using a sample of 406 038 entries of clinical trial data for over 21 143 compounds from January 1, 2000 to October 31, 2015, we estimate aggregate clinical trial success rates and durations. We also compute disaggregated estimates across several trial features including disease type, clinical phase, industry or academic sponsor, biomarker presence, lead indication status, and time. In several cases, our results differ significantly in detail from widely cited statistics. For example, oncology has a 3.4% success rate in our sample vs. 5.1% in prior studies. However, after declining to 1.7% in 2012, this rate has improved to 2.5% and 8.3% in 2014 and 2015, respectively. In addition, trials that use biomarkers in patient-selection have higher overall success probabilities than trials without biomarkers.
          Article 0 comments Cited 453 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival.

            Dik Kwekkeboom, Wouter de Herder, Boen L r Kam … (2008)
            Despite the fact that most gastroenteropancreatic neuroendocrine tumors (GEPNETs) are slow-growing, median overall survival (OS) in patients with liver metastases is 2 to 4 years. In metastatic disease, cytoreductive therapeutic options are limited. A relatively new therapy is peptide receptor radionuclide therapy with the radiolabeled somatostatin analog [(177)Lu-DOTA(0),Tyr(3)]octreotate. Here we report on the toxicity and efficacy of this treatment, performed in over 500 patients. Patients were treated up to a cumulative dose of 750 to 800 mCi (27.8-29.6 GBq), usually in four treatment cycles, with treatment intervals of 6 to 10 weeks. Toxicity analysis was done in 504 patients, and efficacy analysis in 310 patients. Any hematologic toxicity grade 3 or 4 occurred after 3.6% of administrations. Serious adverse events that were likely attributable to the treatment were myelodysplastic syndrome in three patients, and temporary, nonfatal, liver toxicity in two patients. Complete and partial tumor remissions occurred in 2% and 28% of 310 GEPNET patients, respectively. Minor tumor response (decrease in size > 25% and < 50%) occurred in 16%. Median time to progression was 40 months. Median OS from start of treatment was 46 months, median OS from diagnosis was 128 months. Compared with historical controls, there was a survival benefit of 40 to 72 months from diagnosis. Treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate has few adverse effects. Tumor response rates and progression-free survival compare favorably to the limited number of alternative treatment modalities. Compared with historical controls, there is a benefit in OS from time of diagnosis of several years.
            Article 0 comments Cited 355 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): an introduction to the scientific issues.

              Søren Bentzen, Louis Constine, Joseph O. Deasy … (2010)
              Advances in dose-volume/outcome (or normal tissue complication probability, NTCP) modeling since the seminal Emami paper from 1991 are reviewed. There has been some progress with an increasing number of studies on large patient samples with three-dimensional dosimetry. Nevertheless, NTCP models are not ideal. Issues related to the grading of side effects, selection of appropriate statistical methods, testing of internal and external model validity, and quantification of predictive power and statistical uncertainty, all limit the usefulness of much of the published literature. Synthesis (meta-analysis) of data from multiple studies is often impossible because of suboptimal primary analysis, insufficient reporting and variations in the models and predictors analyzed. Clinical limitations to the current knowledge base include the need for more data on the effect of patient-related cofactors, interactions between dose distribution and cytotoxic or molecular targeted agents, and the effect of dose fractions and overall treatment time in relation to nonuniform dose distributions. Research priorities for the next 5-10 years are proposed. Copyright 2010 Elsevier Inc. All rights reserved.
              Article 0 comments Cited 262 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                George Sgouros:
                ORCID: http://orcid.org/0000-0002-4553-2866
                gsgouros@jhmi.edu
                Journal
                Journal ID (nlm-ta): Nat Rev Drug Discov
                Journal ID (iso-abbrev): Nat Rev Drug Discov
                Title: Nature Reviews. Drug Discovery
                Publisher: Nature Publishing Group UK (London )
                ISSN (Print): 1474-1776
                ISSN (Electronic): 1474-1784
                Publication date (Electronic): 29 July 2020
                Pages: 1-20
                Affiliations
                [1 ]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Johns Hopkins University School of Medicine, ; Baltimore, MD USA
                [2 ]ISNI 0000 0001 2171 9952, GRID grid.51462.34, Memorial Sloan Kettering Cancer Center, ; New York, NY USA
                Author information
                http://orcid.org/0000-0002-4553-2866
                http://orcid.org/0000-0001-6930-7383
                http://orcid.org/0000-0002-3465-1296
                Article
                Publisher ID: 73
                DOI: 10.1038/s41573-020-0073-9
                PMC ID: 7390460
                PubMed ID: 32728208
                SO-VID: 51d34a50-b9ec-435f-88a2-c13f4d8d278c
                Copyright © © Springer Nature Limited 2020
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date accepted : 8 June 2020
                Categories
                Subject: Review Article

                Keywords: drug delivery,targeted therapies,radiotherapy
                Data availability:
                Keywords: drug delivery, targeted therapies, radiotherapy

                Comments

                Comment on this article

                scite_

                Similar content578

                See all similar

                Cited by177

                See all cited by

                Most referenced authors3,200

                See all reference authors