Clinical impact of dose reductions and interruptions of second‐generation tyrosine kinase inhibitors in patients with chronic myeloid leukaemia | Zendy

Santos Fabio P. S. | Zendy; Kantarjian Hagop | Zendy; Fava Carmen | Zendy; O’Brien Susan | Zendy; GarciaManero Guillermo | Zendy; Ravandi Farhad | Zendy; Wierda William | Zendy; Thomas Deborah | Zendy; Shan Jianquin | Zendy; Cortes Jorge | Zendy

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Clinical impact of dose reductions and interruptions of second‐generation tyrosine kinase inhibitors in patients with chronic myeloid leukaemia

Author(s) -

Santos Fabio P. S.,

Kantarjian Hagop,

Fava Carmen,

O’Brien Susan,

GarciaManero Guillermo,

Ravandi Farhad,

Wierda William,

Thomas Deborah,

Shan Jianquin,

Cortes Jorge

Publication year - 2010

Publication title -

british journal of haematology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.907

H-Index - 186

eISSN - 1365-2141

pISSN - 0007-1048

DOI - 10.1111/j.1365-2141.2010.08245.x

Subject(s) - medicine , nilotinib , dasatinib , chronic myeloid leukaemia , tyrosine kinase inhibitor , oncology , tyrosine kinase , survival analysis , imatinib , myeloid leukemia , cancer , receptor

Summary Second (2nd)‐generation tyrosine kinase inhibitors (TKI) (dasatinib, nilotinib) are effective in patients with all phases of chronic myeloid leukaemia (CML). Dose reductions and treatment interruptions are frequently required due to toxicity, but their significance is unknown. We analysed the impact of dose reductions/interruptions and dose intensity of 2nd‐generation TKI on response and survival. A total of 280 patients with CML (all phases) were analysed. Dose reductions were considered when the daily dose was below the standard dose. Dose intensity was determined based on the percentage of the ideal dose intensity. Overall, 176 patients (63%) required treatment interruptions and/or dose reduction at least once during therapy. Dose reductions/interruptions, analysed as a time‐dependent covariate, were associated with worse failure‐free survival only in patients with untreated CML. Dose intensity analysis did not reveal a worse response or survival in patients who received a lower dose intensity (<100%) during therapy or during the first 6 months. In conclusion, dose reductions and treatment interruptions of 2nd generation TKI in patients with CML have a minimal impact in the response rate and survival of these patients. Further studies are required to determine whether there might be a minimum adequate dose of these agents.

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