Affiliation:
1. From the Nottingham City Hospital, Nottingham; Royal Marsden Hospital, London, United Kingdom; Innere Klinik und Poliklinik (Tumorforschung), Universitätsklinikum Essen, Essen; Frauenklinik Rotes Kreuz, Munich; Klinik für Tumorbiologie, Freiburg; Stadtische Kliniken Oldenburg, Oldenburg; Albert Ludwigs-Universität Freiburg, Freiburg, Germany; Institut Jules Bordet, Brussels, Belgium; Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser-Franz-Josef-Spital, Vienna, Austria; Kantonsspital St....
Abstract
Purpose 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. Patients and Methods 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. Results 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%). Conclusion 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.
Publisher
American Society of Clinical Oncology (ASCO)
Cited by
420 articles.
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