Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer - PubMed (original) (raw)
Clinical Trial
. 2005 Aug 10;23(23):5314-22.
doi: 10.1200/JCO.2005.66.130. Epub 2005 Jun 13.
Max E Scheulen, Stephen Johnston, Klaus Mross, Fatima Cardoso, Christian Dittrich, Wolfgang Eiermann, Dagmar Hess, Rudolph Morant, Vladimir Semiglazov, Markus Borner, Marc Salzberg, Valerijus Ostapenko, Hans-Joachim Illiger, Dirk Behringer, Nathalie Bardy-Bouxin, Joseph Boni, Steven Kong, Maria Cincotta, Laurence Moore
Affiliations
- PMID: 15955899
- DOI: 10.1200/JCO.2005.66.130
Clinical Trial
Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer
Stephen Chan et al. J Clin Oncol. 2005.
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.
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