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Acute Leukemias

A phase I study of tipifarnib combined with conventional induction and consolidation therapy for previously untreated patients with acute myeloid leukemia aged 60 years and over

Leukemia volume 23, pages 631–634 (2009)Cite this article

Abstract

Patients aged 60 years and over with previously untreated acute myeloid leukemia were enrolled in a Phase I study combining tipifarnib with standard induction therapy. The regimen consisted of cytarabine 100 mg/m2/day continuous intravenous (i.v.) infusion on days 1–7, daunorubicin 60 mg/m2/day i.v. push × 3 on days 6–8 and tipifarnib twice daily on days 6–15. Tipifarnib was escalated over four dose levels (200, 300, 400 and 600 mg). Patients achieving complete response (CR) were eligible to receive one consolidation using the same regimen. The following dose-limiting toxicities (DLTs) were identified during induction: dose level I: 2/6 (hyperbilirubinemia, respiratory arrest), level II: 0/3, level III: 0/3 and level IV: 4/10 (one each of diarrhea, neutropenic enterocolitis, arrhythmia and delayed hematologic recovery post-consolidation). There were no DLTs due to delayed hematologic recovery post-induction. Of 22 evaluable patients, there were 10 CR, 2 morphologic leukemia-free state (MLFS), 2 partial remission (PR) and 8 non-responders. Of seven patients with adverse risk cytogenetics, there were four CR/MLFS and one PR. In summary, this regimen was well tolerated and the maximum tolerated dose was not reached, although somewhat more severe gastrointestinal toxicity was seen at dose level IV. Tipifarnib 600 mg b.i.d. is considered the recommended dose for further study using this regimen.

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Authors and Affiliations

  1. Department of Medical Oncology and Hematology, University of Toronto, Princess Margaret Hospital, Toronto, Canada

    J M Brandwein, A D Schimmer, A C Schuh, V Gupta, K W L Yee, M Moore, K MacAlpine & M D Minden

  2. Department of Medicine, Hamilton Health Sciences, Hamilton, Canada

    B F Leber

  3. Department of Medicine, London Health Sciences Centre, London, Canada

    K Howson-Jan

  4. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    J Wright

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  1. J M Brandwein
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Correspondence to J M Brandwein.

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Brandwein, J., Leber, B., Howson-Jan, K. et al. A phase I study of tipifarnib combined with conventional induction and consolidation therapy for previously untreated patients with acute myeloid leukemia aged 60 years and over. Leukemia 23, 631–634 (2009). https://doi.org/10.1038/leu.2008.341

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