{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:49:25Z","timestamp":1791258565441,"version":"4.1.0"},"reference-count":24,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"23","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2005,8,10]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> In this study, two doses of temsirolimus (CCI-779), a novel inhibitor of the mammalian target of rapamycin, were evaluated for efficacy, safety, and pharmacokinetics in patients with locally advanced or metastatic breast cancer who had been heavily pretreated. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Patients (n = 109) were randomly assigned to receive 75 or 250 mg of temsirolimus weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, adverse events, and pharmacokinetics of temsirolimus. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Temsirolimus produced an objective response rate of 9.2% (10 partial responses) in the intent-to-treat population. Median time to tumor progression was 12.0 weeks. Efficacy was similar for both dose levels but toxicity was more common with the higher dose level, especially grade 3 or 4 depression (10% of patients at the 250-mg dose level, 0% at the 75-mg dose level). The most common temsirolimus-related adverse events of all grades were mucositis (70%), maculopapular rash (51%), and nausea (43%). The most common, clinically important grade 3 or 4 adverse events were mucositis (9%), leukopenia (7%), hyperglycemia (7%), somnolence (6%), thrombocytopenia (5%), and depression (5%). <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> In heavily pretreated patients with locally advanced or metastatic breast cancer, 75 and 250 mg temsirolimus showed antitumor activity and 75 mg temsirolimus showed a generally tolerable safety profile. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2005.66.130","type":"journal-article","created":{"date-parts":[[2005,6,15]],"date-time":"2005-06-15T03:44:08Z","timestamp":1118807048000},"page":"5314-5322","source":"Crossref","is-referenced-by-count":383,"title":["Phase II Study of Temsirolimus (CCI-779), a Novel Inhibitor of mTOR, in Heavily Pretreated Patients With Locally Advanced or Metastatic Breast Cancer"],"prefix":"10.1200","volume":"23","author":[{"given":"Stephen","family":"Chan","sequence":"first","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max E.","family":"Scheulen","sequence":"additional","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Johnston","sequence":"additional","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Mross","sequence":"additional","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Cardoso","sequence":"additional","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Dittrich","sequence":"additional","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Eiermann","sequence":"additional","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Hess","sequence":"additional","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolph","family":"Morant","sequence":"additional","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Semiglazov","sequence":"additional","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Borner","sequence":"additional","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Salzberg","sequence":"additional","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerijus","family":"Ostapenko","sequence":"additional","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Joachim","family":"Illiger","sequence":"additional","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Behringer","sequence":"additional","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Bardy-Bouxin","sequence":"additional","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Boni","sequence":"additional","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Kong","sequence":"additional","affiliation":[{"name":"From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universit\u00e4tsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik f\u00fcr Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universit\u00e4t Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; 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