Originally published as JCO Early Release 10.1200/JCO.2005.66.130 on June 13 2005

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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, 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

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. Gallen, St. Gallen; Inselspital Bern, Bern; Universitätsspital Basel, Basel, Switzerland; N.N. Petrov Research Institute of Oncology, St Petersburg, Russia; Institute of Oncology, Vilnius University, Vilnius, Lithuania; Wyeth Research, Paris, France, Collegeville, PA, and Cambridge, MA; and Central European Society for Anticancer Drug Research-EWIV (CESAR)

Address reprint requests to Stephen Chan, MD, Department of Clinical Oncology, Nottingham City Hospital, Hucknall Rd, Nottingham N65 1PB, United Kingdom; e-mail: schan2{at}ncht.trent.nhs.uk.

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.

Supported by research funding from Wyeth Research, Collegeville, PA.

Presented in part at the 38th Annual Meeting of the American Society of Clinical Oncology (ASCO), Orlando, FL, May 18-21, 2002, and the 39th Annual Meeting of ASCO, Chicago, IL, May 31-June 1, 2003.

Terms in blue are defined in the glossary, found at the end of this issue and online at www.jco.org.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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