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A pilot trial of the mTOR (mammalian target of rapamycin) inhibitor RAD001 in patients with advanced B-CLL

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Abstract

Although B-cell chronic lymphocytic leukemia (CLL) is treatable, it remains an incurable disease and most patients inevitably suffer relapse. Many therapeutic options exist for those requiring therapy, including monoclonal antibodies and stem cell transplantation, but remissions tend to last shorter in the course of the disease. Targeting the cell cycle has recently been realized to be an attractive therapeutic approach in solid and hematological malignancies, and the proliferative nature of B-CLL is increasingly accepted. Here, we report data on a phase II pilot trial with the oral mammalian target of rapamycin (mTOR) inhibitor RAD001 5 mg/daily in patients with advanced B-CLL who had progressive disease after at least two lines of treatment. After treatment of seven patients, this trial was stopped because of toxicity concerns, although some degree of activity was observed (one partial remission, three patients with stable disease). Interestingly, cyclin E expression decreased in responding patients. Further strategies of mTOR inhibition by RAD001 in B-CLL should focus on different treatment schedules, adequate anti-infectious prophylaxis, or combinations with cytotoxic drugs.

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Authors and Affiliations

  1. III. Department of Medicine, Technical University of Munich, Ismaningerstr. 15, 81675, Munich, Germany

    Thomas Decker, Katharina Goetze, Madlen Oelsner, Ingo Ringshausen & Christian Peschel

  2. Onkologie Ravensburg, Wilhelm Hauff Str 41, 88212, Ravensburg, Germany

    Thomas Decker

  3. Onkologische Gemeinschaftspraxis Weilheim, Weilheim, Germany

    Michael Sandherr

Authors
  1. Thomas Decker
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  2. Michael Sandherr
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  3. Katharina Goetze
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  4. Madlen Oelsner
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  5. Ingo Ringshausen
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  6. Christian Peschel
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Corresponding author

Correspondence to Thomas Decker.

Additional information

T.D., M.S., and K.G. contributed to the clinical care of the patient and interpretation of data. M.O. carried out laboratory investigations and contributed to analysis of data. T.D., M.S., and C.P. designed the study. T.D. wrote the paper.

This work was supported in part by funding from Novartis Pharma.

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Decker, T., Sandherr, M., Goetze, K. et al. A pilot trial of the mTOR (mammalian target of rapamycin) inhibitor RAD001 in patients with advanced B-CLL. Ann Hematol 88, 221–227 (2009). https://doi.org/10.1007/s00277-008-0582-9

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  • DOI: https://doi.org/10.1007/s00277-008-0582-9

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